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Why does sympathetic activity constrict pulmonary vessels?

Why does sympathetic activity constrict pulmonary vessels?



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I don't know understand why sympathetic stimulation constricts pulmonary vessels? I thought that the sympathetic nervous system activated the body for physical activity. Physical activity would need more oxygen supply. Doesn't constriction of pulmonary vessels reduce the gas exchange?


Short answer
The sympathetic nervous system mediates the fight, flight and fright response. It constricts the arteries and arterioles to increase blood pressure, in turn pushing the blood to the muscles and other organs vital for physical activity.

Background
The sympathetic nervous system functions triggers the fight, fright, flight (FFF) response (Fig. 1). It provides the body with a burst of energy so that it can respond to danger (source: Harvard Medical School).

The FFF response is initiated in the hypothalamus by activating the sympathetic nervous system through the adrenal glands. These glands release epinephrine (adrenaline) into the bloodstream. Epi increases heart rate and blood pressure to push blood to the muscles, heart, and other vital organs. The person also starts to breathe more rapidly and the small airways in the lungs open up. This way, the lungs can take in as much oxygen as possible with each breath. Extra oxygen is sent to the brain, increasing alertness (source: Harvard Medical School).

In blood vessels, as you say, sympathetic activation constricts arteries and arterioles (resistance vessels), which increases vascular resistance and decreases distal blood flow. When this occurs throughout the body, the increased vascular resistance causes arterial pressure to increase (Klabunde, 2012). This enhances the distribution of oxygen already present in the blood. I don't think the pulmonary circulation responds differently than that in the rest of the body. The stress response is meant to support the evasion of acute dangers. But indeed, chronic exposure to adrenaline may eventually lead to impaired oxygen exchange in the lungs (Krishnamoorthy et al., 2012).


Fig. 1. Fight, flight, fright response. source: Freelap USA

References
- Klabunde, Cardiovascular Physiology Concepts, 2nd ed. (2012). Lippincott Williams & Wilkins
- Krishnamoorthy et al., Anesthesiology (2012); 117(10): 745-54


Physiology of the Normal Pulmonary Circulation

Hypoxia

There is an active intrapulmonary control mechanism able to some extent to correct the passive gravity-dependent distribution of pulmonary blood flow: a decrease in PO2 increases pulmonary vascular tone. Hypoxic pulmonary vasoconstriction was first demonstrated by von Euler and Liljestrand (1946) . The authors proposed a functional interpretation that can still be considered valid. As schematically summarized by Hughes (1975) , PO2 in lung tissue is determined by a ratio between O2 carried to the lung by alveolar ventilation (VA) and O2 carried away from the lung by blood flow (Q)

In contrast with hypoxic vasodilation in systemic tissue, where local PO2 is accordingly determined by a ratio flow of O2 carried to the tissues (Q) and local O2 consumption (VO2)

Hypoxic pulmonary vasoconstriction has been at the origin of a huge amount of research extending over decades ( Sylvester et al., 2012 ). This is explained by the simplicity and accessibility of the pulmonary circulation as a research model for physiological and biological studies, and the belief that understanding the mechanisms of hypoxic vasoconstriction would offer the perspective of curing pulmonary hypertension. What has been learned since the initial observation of von Euler and Lilistrand can be summarized as follows:

The hypoxic pulmonary pressor response is universal in mammals and in birds, but with considerable inter-species and inter-individual variability. It is intense in pig, horse and cow, mild to moderate in rodents and humans and very low in dog, guinea pig, yak and llama.

Chronic hypoxia induces pulmonary hypertension, in proportion to initial vasoconstriction, and is not immediately reversible at reoxygenation.

Initial hypoxic vasoconstriction is a quasi-immediate response with subsequent modulation depending on the experimental model or preparation.

Hypoxic vasoconstriction strengthens during the first few hours of hypoxic exposure in humans.

The reversibility of increased PVR with re-oxygenation is largely lost after 24–48 h exposure to hypoxia.

Hypoxic vasoconstriction is observed in lungs devoid of nervous connections, and indeed also in isolated pulmonary arterial smooth muscle cells.

Hypoxic vasoconstriction is enhanced by acidosis, a decrease in mixed venous PO2, repeated hypoxic exposure (in some experimental models), perinatal hypoxia, decreased lung segment size, cyclooxygenase inhibition, nitric oxide inhibition, and certain drugs or mediators which include almitrine and low dose serotonin.

Hypoxic vasoconstriction is inhibited by alkalosis, hypercapnia without associated acidosis, an increase in pulmonary vascular or alveolar pressures, vasodilating prostanoids, nitric oxide, complement activation, low dose endotoxin, calcium channel blockers, β2 stimulants, nitroprusside, and, paradoxically, by peripheral chemoreceptor stimulation.

The hypoxic pressor response is biphasic, with a progressive increase as PO2 is progressively decreased to approximately 35–40 mmHg, followed by a decrease (“hypoxic vasodilatation”) in more profound hypoxia.

The hypoxia-induced increase in PVR is mainly caused by a constriction of pre-capillary small arterioles. Small pulmonary veins also constrict in response to hypoxia, but this should not normally contribute to more than 20–30% of the total change in PVR.

While hypoxic pulmonary vasoconstriction has been shown to be an only moderately efficient feedback mechanism ( Grant, 1982 ) it may still produce substantial improvements in arterial oxygenation of patients with inhomogeneous lungs such as in chronic obstructive pulmonary disease (hypoxemia mainly explained by low ventilation/perfusion ratios) or in the acute respiratory distress syndrome (hypoxemia mainly explained by ventilation/perfusion ratios equal to zero, or shunt) ( Brimioulle et al., 1996 ).

The biochemical mechanism of hypoxic pulmonary vasoconstriction remains incompletely understood ( Sylvester et al., 2012 ). Current thought is that a decrease in PO2 inhibits smooth muscle cell voltage-gated potassium channels, resulting in membrane depolarization, influx of calcium, and cell shortening. However, the nature of the low PO2 sensing mechanism remains elusive. Mitochondria and nicotinamide adenine dinucleotide phosphate oxidases are discussed as oxygen sensors. Reactive oxygen species, redox couples and adenosine monophosphate-activated kinases are candidate mediators. The reversal of hypoxic vasoconstriction by profound hypoxia is due to an activation of ATP-dependent potassium channels.

Hypoxic pulmonary vasoconstriction serves to limit the perfusion of fetal lungs. There has been no demonstration that hypoxic pulmonary vasoconstriction matters to the outcome of lung diseases. Persistent whole lung hypoxic vasoconstriction at high altitudes may be a cause of “fixed” pulmonary hypertension in proportion to initial pressor response ( Reeves et al., 1979 ). High altitude pulmonary hypertension is generally mild or borderline in the human species ( Soria et al., 2016 ) and thus of uncertain clinical relevance.


Pulmonary Circulation: Anatomy and Peculiarities | Humans | Biology

Blood enters lungs through two sources pulmonary artery and bronchial arteries. The cross-sectional area of the pulmonary artery is same as that of the aorta, but it is more elastic and distensible. Through the pulmonary artery venous blood of the right ventricle goes to the lungs for oxygenation. It also carries nutrition to the pulmonary tissues. Bronchial arteries, originating from the aorta, carry oxygenated blood for the nutrition of bronchi and bronchioles (Fig. 7.104).

The pulmonary artery breaks up into wide arterioles and capillaries which form a rich network surrounding the alveoli where gaseous exchange takes place. The bronchial artery also breaks up into capillaries which partly join the alveolar network but is mostly returned through bronchial veins and partly through azygos vein.

The branches of the bronchial artery are also distributed to the bronchial glands and walls of the bronchioles as well as respiratory bronchioles and thus form capillary plexuses which drain blood into the pulmonary venules (Fig. 7.105). The oxygen supply to the pulmonary tissues comes from the deoxygenated blood as well as from the oxygenated blood.

Method of Recording Pulmonary Arterial Pressure:

With the help of the cardiac catheter—it is inserted through the systemic vein into the right atrium and then into the right ventricle and then into the pulmonary artery from where the pulmonary arterial pressure can be recorded.

Vasomotor Supply:

The sympathetic supply is from upper thoracic segments and the parasympathetic supply from the vagus. Results of stimulation of nerves are variable. Stimulation of the chemoreceptors of the carotid body causes diminution of the pulmonary vascular resistance which disappears after section of the vagus and the sympa­thetic. So pulmonary circulation is under reflex control.

Normal Values of Pulmonary Circulation:

It is the sum total of right ventricular output and blood flow through the bronchial arteries. Hence a little over 4-5 litres.

The systolic pressure in the human pulmonary artery is about 22 mm of Hg (right ventricle—about 22 mm of Hg). The diastolic pressure is about 10 mm of Hg (right ventricle 0 to 1 mm of Hg). With each heart beat the pressure rises in the pulmonary artery and thus causes pulsation in these vessels. The pulmonary capillary pressure is about 8 mm of Hg. The pulmonary venous pressure is about 5 mm of Hg (left atrium—approximately 4 mm of Hg).

Functions of Pulmonary Circulation:

It is the main function of the pulmonary circulation. Through circulation the mixed deoxygenated blood is passed through alveolar capillaries and thus gaseous exchange in between the alveolar air and alveolar capillaries takes place. Due to gaseous exchange, blood that passes through alveolar capillaries gets proper amount of O2, and gets rid of proper amount of CO2.

The fine pulmonary blood vessels act as a filter. It traps the emboli that pass through the pulmonary capillaries. Thus filter prevents from reaching and blocking the vessels in the brain and heart.

Pulmonary circulation maintains the nutrition of the lung tissue.

Pulmonary capillary pressure is very low which tends to pull fluid from the alveoli and thus any fluid accumulation in the alveoli is speedily absorbed into the blood. This phenomenon has been observed by Cohn (1873). He introduced 25 litres of water through the trachea slowly and observed no discomfort in the Animals. Of course, rapid absorption of water in the blood may cause haemolysis and at the same time may increase the work load of the heart due to increase of plasma volume.

v. Reservoir for Left Ventricle:

Left ventricular output is fully dependent upon the return of blood from the pulmonary bed to the left atrium. So any alteration of the pulmonary haemodynamics will alter the left ventricular function.

Control of Pulmonary Circulation:

The amount of blood passing through lungs follows the same general principles as elsewhere.

It depends upon the following factors:

i. Output of the Right Ventricle (Mechanical Factor):

It depends upon the force and frequency of contraction and the degree of venous return. Cardiac output may increase 3 or 4 times but the pulmonary arterial pressure does not rise appreciably.

ii. Resistance of the Pulmonary Bed: It depends upon the following factor- (a) Lumen of the pulmonary vessels- Hypoxia produces pulmonary vasoconstriction. Increased CO2 tension in the blood constricts the pulmonary blood vessels. It has been observed that if one lung is ventilated with a mixture of CO2 and O2, and the other lung with air then most of the blood is shifted to the normally ventilated lung so as to protect the body from hypercapnoic effect. This is auto-regulation of pulmonary blood flow.

Adrenaline and noradrenaline also produce vasoconstriction. Acetyl-choline also dilates the pulmonary blood vessels but the degree of vasodialtion is mostly dependent upon pre-existing tone of the smooth muscle of the pulmonary blood vessel. Serotonin, a humoral substance originating from disintegrating platelets or by secretory products of chromaffin tissues also constricts the pulmonary blood vessels. Recently it has been observed that the emboli in the pulmonary capillaries produce reflex vasoconstriction of the pulmonary arterioles.

This, according to some physiologist, is due to – (a) Stimulation of the vagal receptor lying near these small vessels. The receptors respond to 5-hydroxytryptamine (serotonin) released from the platelets near the emboli. (b) Condition of the lungs—Fibrosis, emphysema (overstretching), pneumonia, etc., increase the resistance, (c) Condition of the heart—Mitral stenosis of left heart failure retards venous out-flow from the lung and increases the pulmonary resistance, and (d) Respiration.

iii. Role of Respiration:

During inspiration, the pulmonary bed enlarges, capillary pressure falls to about —2 mm of Hg and therefore more blood enters the lungs. This is caused by elongation of the capillaries due to stretching and their dilatation due to negative pressure and probably vasomotor effect. Thus during inspiration, lungs can hold about 10% of total blood volume.

During expiration, reverse changes take place, pressure rises to about 4 mm of Hg and lungs can hold only about 6% of the blood volume. But total pulmonary vascular resistance increases during both maximal inflation and forced deflation of the lungs. Measurement of vital capacity acts as a guide. A fall shows pulmonary congestion.

The pulmonary blood vessels have got both parasympathetic and sympathetic nerve supply. But there is still doubt that these nerve supplies have got any major physiological role in main­tenance of normal circulation. Gracia Ramos and Rudomin (1957) have claimed the presence of active nervous control of the pulmonary blood vessels as they have observed reduction in O2, saturation of arterial blood following stimulation of the sympathetic nerve. Electrical stimulation of caudal end of cut cervical vago-sympathetic nerve also causes vasodilatation which is observed following administration of atropine.

The pulmonary circulation is also modified through reflexes originated due to stimulation of baroreceptors and present in the Sino-aortic areas. Stimulation of baro-receptors in the carotid sinus and aortic arch produces reflex vasodilatation in the pulmonary vascular bed, whereas stimulation of chemoreceptors in the aortic bodies or carotid bodies produces pulmonary vasoconstriction.

Peculiarities of Pulmonary Circulation:

i. Pulmonary artery carries deoxygenated blood and pulmonary veins carry oxygenated blood.

ii. Filtration of fluid in systemic capillaries filtration of fluid takes place into the tissue space, but, nothing such happens in the lungs. The purpose is obvious. Filtration would cause collection of liquid in the alveoli and retard oxygenation of blood. The mechanism is also obvious.

In the pulmonary capillaries the colloidal osmotic pressure (25 mm of Hg) is much higher than the blood pressure. In the systemic capillaries it is just the reverse. Hence, no filtration in the lungs. Pulmonary congestion, from any cause, will increase the local blood pressure leading to filtration and causing oedema of lungs.

iii. Filtration of emboli the fine pulmonary capillary acts as a filter that traps emboli from reaching and blocking the blood vessels of heart, brain or other organs.

iv. Blood enters lungs through pulmonary and bronchial arteries. Blood is returned from the lungs through similar two channels the pulmonary veins (oxygenated blood) and bronchial veins (reduced blood). One may think that the reduced blood instead of being returned through the bronchial veins could have easily joined the alveolar capillaries, become oxygenated and be returned through the pulmonary veins to the left heart.

But in that case the venous return to the left heart would be more than the output of the right heart. This discrepancy may lead to heart failure. Only that amount of blood which was expelled by the right heart will return to the left heart, so that the output of the two ventricles may remain same. Thus blood flow through the two systems—pulmonary and systemic, are equal.

v. The pulmonary vascular bed is a low, resistance circuit, whereas the systemic one is a high resistance circuit.

vi. Pulmonary vascular bed has to supply blood to one type of tissue, whereas the systemic one has to supply blood to different types of tissues.

vii. Pulmonary vascular bed is relatively short distensible with large calibre and can accommodate a large volume of blood (blood reservoir).

viii. As the pulmonary vascular bed is exposed to sub-atmospheric pressure, the pulmonary pressure and flow are altered during inspiration and expiration.

ix. As the pulmonary vascular bed is short and distensible, blood flow is not fully dependent upon neurogenic control and mechanical factor of the right heart plays an important role in maintenance of normal blood flow.

x. Local actions of CO2 and low O2 on the pulmonary vascular bed are of vasoconstrictions which are just the reverse in case of the systemic one.

xi. Though the pulmonary vascular bed has got both sympathetic and parasympathetic innervations, yet its role in the maintenance of circulation is less important than the systemic one.

Effect of Respiration on the Systemic Blood Pressure:

Generally systemic blood pressure falls during inspiration and rises during expiration. This is due to increased capacity of the pulmonary vascular bed during inspiration holding a larger volume of blood and thus momentarily reducing the return of blood to the left heart. Because during inspiration, pulmonary vascular resistance is greatly reduced as the intrathoracic pressure is below the atmospheric pressure.

So at the first phase of inspiration, aortic pressure is decreased and at the last phase of inspiration as well as with the onset of expiration the systemic pressure is increased. Because venous returns to the left heart is gradually increased at the later phase of inspiration and towards the early phase of expiration.

1. Pulmonary Vascular Reflex:

There are baroreceptor areas in the pulmonary arch of aorta and when these receptors are stimulated, reflexly alter the systemic blood pressure, heart rate and capacity of the peripheral blood vessels. An increase in the pulmonary arterial pressure produces reflex bradycardia, hypotension and increase of blood flow in the splanchnic bed.

These responses are abolished following divisions of the vagus nerves:

i. Reflexes from the pulmonary vascular bed may participate in the regulation of blood volume. Increased blood volume in the thoracic cavity reflexly produces diuresis through the inhibition of the antidiuretic hormone (ADH) secretion.

ii. Intravenous injection of starch grain, multiple emboli may produce rapid shallow breathing. This reflex respiratory response is due to the stimulation of receptors in the pulmonary vascular bed and can be abolished following section of the vagi.

2. Pulmonary Depressor Chemoreflex:

Intravenous injection of phenyl diguanide induces bradycardia and hypotension. It has been claimed that these reflex effects are initiated through the stimulation of pulmonary deflation receptors. Likewise serotonin, starch grain, multiple emboli stimulate these deflation receptors and induce pulmonary depressor chemoreflex.

Circulatory Status in Different Cardiopulmonary Diseases:

1. Mitral Stenosis:

It is the condition when the orifice of the valve is narrowed by fusion of the cusp margins. The cusps become rigid and thickened. The chordae tendineae hold the valve in a fixed position and the opening becomes narrowed. The whole ring looks like a narrow rigid funnel. Due to narrowing of the opening, a resistance is offered for blood flow from the left atrium to the left ventricle. The left atrium is dilated and thickened due to accumulation of blood within itself.

Furthermore the great problem that arises due to this is the occurrence of pulmonary hypertension. With the obstruction of blood flow from the left atrium to the left ventricle, the left atrial pressure is tremendously increased causing decrease in pulmonary driving force. So the consequence is the decrease in pulmonary flow, right ventricular hypertrophy or cor pulmonale ultimately leading to right heart failure.

It is the condition in which there is enlargement of the air spaces distal to the terminal bronchiole. Obstruction to expiration due to oedema, inflammatory changes or mucus in the bronchi may cause emphysema. In emphysema, pulmonary vascular resistance is greatly enhanced causing obstruction to blood flow.

Ultimately, the pulmonary hypertension and then right heart failure may occur. The increase of pulmonary vascular resistance is the consequence of destruction of blood vessels. Poor exchange of air in the emphysematous alveoli may also cause increase of vascular resistance by accumulated CO2 in the blood.

3. Pulmonary Embolism:

In pulmonary embolism either massive or diffuse, the blood flow is greatly affected due to blockade of pulmonary blood vessels by free-moving clot (embolus).

It is the condition when a lung or a part of a lung remains in a collapsed state. In pneumothorax that is when the chest cavity is opened to atmospheric pressure. In such condition, the pulmonary vascular resistance is greatly increased causing the decrease of pulmonary blood flow.

In natural atelectasis, the alveoli not only constrict, blood vessels lining the alveoli are also constricted causing vascular detachment with the rest of the lung. This is a safety mechanism of the lung so that the ill-ventilated lung is prevented from supplying major quantities of blood.

5. Removal of Lung:

In case of pneumectomy or lobectomy, pulmonary haemodynamics remain unaltered so long the subject maintains a sedentary life. But if the subject performs heavy work then due to increase of cardiac output, the pulmonary pressure may be increased drastically because in such subject the pulmonary reserve is very low.

6. Diffuse Sclerosis of Lung Vessels:

In sclerosis of the pulmonary blood vessels the elasticity as well as the distensibility of the lung vessels is decreased. Pulmonary vascular capacity is also affected greatly. In such case if subjects do not have such heavy or even mild work so that the cardiac output is increased, then there should have no trouble. In late or extreme stages of sclerosis, the pulmonary blood flow is greatly decreased and pulmonary hypertension along with the right heart hypertrophy may be happened.

7. Pulmonary Fibrosis:

It is the cause of formation of fibrous tissue during healing of the wound. The generalised fibrosis happens in lung tissue following recovery from tuberculosis, bronchopneumonia, pneumoconiosis, gas poisoning, etc. Under such condition the pulmonary vascular resistance is increased. Thus obstruction to blood flow may be offered causing pulmonary hypertension in late stage.


Mechanism

Hypoxic pulmonary vasoconstriction relies on the appropriate functioning and response of the pulmonary vasculature in the presence of diminished oxygen availability. Approximately 250 million alveoli are present within each lung. Each one is a functional unit that serves to deliver inhaled oxygen from the atmosphere to the blood and expulsion of carbon dioxide from the blood to the atmosphere. The alveoli interact with the pulmonary capillaries, allowing for gas exchange.

Theories of the Vasoconstriction Reflex

The vasoconstriction reflex is triggered in states of hypoxia. There are contrasting views as to the vascular structures that first detect hypoxia. The classical understanding suggests that decreased oxygen levels are initially detected within the pulmonary artery, whereas a new concept postulates that low oxygen levels are detected in theਊlveoli. This latter concept further suggests that gap junctions throughout the pulmonary endothelium transmit signals to the pulmonary arterioles, causing them to constrict.

Original Understanding of the Vasoconstriction Reflex

The original mechanism is thought to involve voltage-gated potassium and calcium channels. These channels are located in the smooth muscle cells of the pulmonary arteries and are very sensitive to low oxygen states. In addition to the critical roles of potassium and calcium in hypoxic pulmonary vasoconstriction, there are indications that there could be other ion channels contributing to the mechanism. These ion channels are transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential canonical 6 (TRPC).[2][5][6]


Size Matters!

The pulmonary vasculature is innervated by specific subsets of sympathetic, parasympathetic, and sensory nerve fibers. In contrast to most other organs, innervation density is highest at large-caliber vessels and decreases toward the periphery, and reactivity to vasoactive compounds also changes along the course. In some species, such as the experimentally widely used rodents rat and mouse, autonomic efferent (sympathetic and parasympathetic) perivascular axons barely reach beyond the lung hilus, whereas in humans this innervation extends to small intrapulmonary vessels. Throughout, the most distal arterioles (i.e., intraacinar arteries equipped with an incomplete coat of intermediate cells instead of a full muscular wall) are devoid of innervation. Altogether, 10 vasoactive substances (3 small molecular transmitters and 7 neuropeptides) at minimum have been identified in various combinations (cotransmission) in pulmonary vascular axons. Analysis of this “neurochemical coding” has been provided only for the guinea pig so far, but not for humans or for animal species commonly used for pulmonary vascular research. Sympathetic pulmonary vascular neurons are reflexively activated via arterial chemoreceptors when arterial P o 2 is lowered and adapt the pulmonary vasculature to this condition of increased pulmonary blood flow by α1-adrenoreceptor–mediated increase in vascular impedance primarily at large vessels. In contrast, neither they nor other nerve fibers play a role in the local hypoxic vasoconstriction triggered by low alveolar P o 2, which serves to match perfusion to ventilation. The major potential role of the pulmonary vascular innervation, autonomic and sensory, lies in the pronounced trophic activities of its transmitters.

As a rule, the vascular bed of every organ is, among additional other factors, regulated by the nervous system, and the lung is not an exception. This widely recognized fact might lead to the assumption that largely uniform principles and mechanisms generally apply to nervous control of blood vessels, but each organ and even each vascular segment within it receives specific types of nerve fibers with specific reflex connectivity, cocktail of transmitters (neurochemical coding), and equipment with transmitter receptors on the target cells. Pulmonary vessels are innervated by autonomic (sympathetic and parasympathetic) and sensory nerve fibers, and these major classes can be further subdivided into distinct subpopulations. A particular feature of pulmonary veins is their sleeve of cardiomyocytes extending from the left atrium. In some animals, this myocardial venous layer extends deep into the lung (1). It can be the site of origin of ectopic excitation leading to atrial fibrillation, and its rich innervation has, therefore, received particular attention in the context of understanding pathogenesis of cardiac arrhythmias (2). It will not be further addressed in the present review, which focuses on regulation of lung perfusion in particular in response to alveolar or arterial hypoxia.

The lung receives axons from principal sympathetic neurons residing in the middle and inferior cervical and the first five thoracic ganglia (including the stellate ganglion), and the vasculature is the major sympathetic target in the lung. “Sympathetic” and “(nor)adrenergic” are often used synonymously to describe these fibers, and indeed the vast majority of pulmonary sympathetic axons do produce and release noradrenaline. Accordingly, all of our histochemical knowledge on the distribution of “sympathetic” axons along the pulmonary vascular tree in fact is based on the demonstration of either noradrenaline itself or its synthesizing enzymes. Still, retrograde neuronal tracing from the guinea pig lung—a technique wherein a fluorescent tracer substance is injected into the peripheral organ (here: lung), taken up by nerve terminals, and transported back to the nerve cell bodies in ganglia and the central nervous system—has identified a small population of lung-projecting sympathetic neurons that is not catecholaminergic (3). It is currently unresolved whether these noncatecholaminergic sympathetic neurons innervate blood vessels or airways or other targets within the lung. On the other hand, catecholamine synthesis is not entirely confined to sympathetic neurons: some principal neurons of local parasympathetic ganglia also express the enzymes necessary for catecholamine synthesis (4), which explains that pulmonary arteries in reimplanted canine lungs, in which only such local parasympathetic neurons survive, still receive noradrenergic nerve fibers (5). These limiting aspects have to be taken into account when interpreting data on the distribution of “sympathetic” axons along the pulmonary vascular bed. Yet, the general conclusions reported below are also in agreement with functional studies using electrical stimulation of sympathetic nerves or equivalent approaches.

Consistent through all species, sympathetic noradrenergic innervation density is highest at large extrapulmonary and hilar blood vessels—both arteries and veins—and then decreases toward the periphery (6–8). This is in marked contrast to many other organs, in which highest innervation density is found at the level of the smallest arterioles (e.g., rat heart) (9). It varies from species to species how far sympathetic noradrenergic axons reach into the lung—in the guinea pig, rabbit, sheep, cat, dog, and human, small arteries down to 50 μm in diameter are innervated (6–8), whereas in rat, mouse, hedgehog, and badger, noradrenergic innervation stops soon after the lung hilus (6, 7)—but the smallest intraacinar arteries are not innervated in any known species ( Figure 1 ).

Figure 1. Schematic representation of the species-specific distribution of sympathetic (Sy red), parasympathetic (P light green: cholinergic, dark green: NOS and VIP) and sensory (Se yellow) nerve fibers along the pulmonary vascular tree, projected onto a micro-computed tomography (CT) image of the arterial tree of a mouse lung. (A) Situation in guinea pig, rabbit, sheep, cat, dog, human. (B) Situation in mouse, rat, hedgehog, badger. Innervation density is reflected by width of the bars. Solitary sensory fibers in the lung parenchyma and located subpleurally are indicated in both groups of species. (CT image provided by Dr. A. Langheinrich, Radiology Department, Justus-Liebig-University Giessen.)

Sympathetic nerve stimulation increases pulmonary vascular resistance and decreases compliance, which is mediated by noradrenaline via α-adrenoreceptors, primarily of the α1-subtype (10).

Noradrenergic sympathetic axons do not represent a homogenous entity. Multiple use of more than one transmitter (cotransmission) is the rule rather than the exception, and functionally distinct subpopulations often differ in the transmitter cocktail they use (neurochemical coding). ATP is stored together and, hence, released together with noradrenaline from sympathetic terminals (11). In addition, sympathetic neurons can synthesize and release certain neuropeptides, the most abundant of which is neuropeptide Y (NPY) (12). This multiplicity of transmitters released from one nerve ending explains why pharmacological blockade of the “classical” transmitter, noradrenaline, alone does not abrogate all effects elicited on nerve stimulation. Purinergic, peptidergic, and other (e.g., those evoked by NO) effects also persist after additional inhibition of cholinergic transmission. Such effects are, by definition, “nonadrenergic, noncholinergic” (NANC). Before recognition of cotransmission in autonomic neurons and of peptide release from sensory neurons, it was suspected that a novel, previously unknown NANC system innervates the lung. In view of the present knowledge, this term shall be abandoned, because (1) the vast majority of nerve fibers indeed can exert NANC effects even if they use noradrenaline (or acetylcholine) as a main transmitter, and (2) this term does not discriminate between neurons that use other transmitters than noradrenaline and acetylcholine in addition to them or alone.

In the axon terminal, neuropeptides are stored in large (approximately 90 nm in diameter) dense core vesicles, which are different from the small (45 nm) synaptic vesicles containing noradrenaline. This allows for differential release of transmitters from one and the same terminal, because exocytosis of dense core vesicles requires high-frequency stimulation of the terminal, whereas the content of small vesicles is already released at much lower stimulation frequencies (13). Hence, the spectrum of effects evoked by a single terminal can depend on the frequency of its stimulation.

An extensive network of noradrenergic and NPY-containing fibers has been noted around pulmonary arteries of several species, but only a few studies used double-labeling techniques to evaluate the extent of colocalization. In the guinea pig, principally all noradrenergic fibers innervating pulmonary arteries and veins contain NPY and, in addition, dynorphin, a neuropeptide of the opioid family (3). In this aspect, pulmonary vascular innervation differs markedly from that of skin arteries in the same species, wherein three different combinations of noradrenaline, NPY, and dynorphin are used by sympathetic axons. Each of these populations is restricted to a specific segment of the arterial tree in the skin (14). Still, noradrenergic and NPY-containing fibers do not match 1:1 in the lung either, as there is a minor population of axons innervating guinea pig pulmonary arteries and veins that contains NPY plus vasoactive intestinal peptide (VIP) but not noradrenaline (3). It remains to be clarified whether this less-frequent fiber population represents the nonnoradrenergic neurons projecting to the guinea pig lung or originates from other systems.

With a pulmonary artery pressure of only about 1/5 but the same flow volume per minute as the systemic circulation, the lung circulation is a low-pressure, low-resistance system. The sympathetic noradrenergic innervation participates in maintenance of basal pulmonary tone, as evidenced by decrease in pulmonary vascular resistance after either surgical sympathectomy or α-adrenoreceptor blockade (reviewed in Reference 10). β-Adrenoreceptor blockade, on the other hand, increases resting pulmonary arterial pressure in dogs, sheep, and humans (10, 15). Not only innervation densities but also vascular reactivity to neurotransmitters varies along the vascular tree. Noradrenergic effects decline concomitant to decline of arterial diameter, and short but strong α1-adrenoreceptor–mediated constrictions can be evoked in extra- but not intrapulmonary arteries (16).

In organ bath experiments, NPY causes contraction of pig pulmonary arteries (17), whereas the contraction of rabbit isolated extra- and intrapulmonary arteries induced by electrical stimulation of nerve terminals does not involve NPY acting on Y1 receptors, which is usually considered to mediate NPY-induced contraction (16). In rabbit intra- and extrapulmonary arteries, electrical stimulation evokes a slow contraction that is resistant to α1-adrenoreceptor and Y1 receptor blockade and is neither mediated by ATP nor by acetylcholine, angiotensins, or endothelin-1. This might be caused by a yet unidentified cotransmitter of sympathetic or other nerve terminals, but the underlying mechanisms yet have to be elucidated (16). Clearly, these data indicate the need for further studies directed toward elucidating the neurochemical coding of pulmonary perivascular axons.

Sympathetic noradrenergic nerve fibers are reflexively activated by distension of the main pulmonary artery (18) or proximal airway segments (cervical trachea, larynx, pharynx) (19). The responses to low arterial P o 2 are due to activation of carotid and/or aortic arterial chemoreceptors and involve both the sympathetic chain and the vagus nerve (10, 20). Reported effects on pulmonary arterial pressure vary considerably depending on conditions of investigation and include increases, no changes, or even decreases in pulmonary vascular resistance (10). Pronounced increases in vascular stiffness are sympathetically driven and occur in several conditions as short-term cold exposure, exercise, and exposure to hypoxia resulting in lowered arterial P o 2 (10, 20). Consequences of such a decrease in compliance are decrease in pulmonary arterial capacitance and increase in input impedance and right ventricular afterload, which have been identified as strong predictors of clinical outcome in patients with pulmonary arterial hypertension (21, 22). Importantly, this hypoxia-induced sympathetic response primarily on central vessels has to be discriminated from hypoxic pulmonary vasoconstriction (HPV), which occurs distally in response to alveolar P o 2. This local vascular response, often referred to as von Euler-Liljestrand reflex, serves to match perfusion to ventilation by shifting blood from poorly ventilated to well-ventilated areas, thereby improving arterial oxygen saturation. Its precise mechanisms have not been unraveled yet. It occurs at vascular segments that are not innervated at all (e.g., at the level of intraacinar arteries) (23, 24), and more upstream, including innervated arteries, involving at least partly different mechanisms at these different vascular segments, but throughout it is a direct vascular response (25, 26). Surgical and chemical (treatment with 6-OHDA) sympathectomy do not affect the increase in pulmonary vascular resistance in response to alveolar hypoxia in dogs, demonstrating the independence of this local HPV from sympathetic innervation (20, 27). Accordingly, bilateral surgical sympathectomy is generally well tolerated in most patients, albeit a case of orthodeoxia (i.e., postural hypoxemia) has been reported and ascribed to a combination of lung collapse/consolidation and blunted HPV (28).

Different scenarios of hypoxia in the lung have to be discriminated: a purely local alveolar hypoxia (e.g., caused by mucus plugging) in an otherwise sufficiently ventilated lung will initiate the classical, nerve-independent von Euler-Liljestrand reflex to match perfusion to ventilation. In global hypoxia (e.g., in high altitude) local HPV causes a general rise in pulmonary arterial pressure but is no longer beneficial. Such conditions and dysregulation of the normally occurring local HPV are considered as a risk or initiating factor of the development of pulmonary hypertension with vascular remodeling (i.e., thickening of all three layers of the vascular wall) (29, 30). Indeed, chronic hypoxia leads to proliferation of endothelial cells, smooth muscle cells, and adventitial cells of pulmonary arteries, including intraacinar vessels, in situ and in cell culture (31, 32).

At the same time, however, sympathetic drive to the more central pulmonary vessels is particularly high due to reflex activation via arterial chemoreceptors. Besides the immediately obvious effects on vascular tone, mediators released by sympathetic axons have pronounced trophic actions on the target tissues. As early as in 1984, McKenzie and Klein noted that exposure of rats to hypobaric hypoxia for 3 to 7 days results in increased wet weight and absolute protein content of the pulmonary trunk, which is largely reduced in animals subjected to neonatal chemical sympathectomy with guanethidine (33). In 1999, Salvi put forward the “α1-adrenergic hypothesis for pulmonary hypertension,” focusing on antiapoptotic and proliferative effects mediated by α1-adrenoreceptors (34). Hypoxia-induced pulmonary vascular remodeling has been systematically investigated in knockout mice lacking dopamine β-hydroxylase, an enzyme necessary for generation of noradrenaline and adrenaline, and the α1-adrenergic receptor subtypes α1B and α1D (35). Hypoxia-induced distal muscularization was strongly inhibited in mice incapable of (nor)adrenaline synthesis and partially inhibited in either of the α1-adrenergic receptor–deficient strains, pointing to a synergistic action of α1B- and α1D-subtypes (35). In rat pulmonary artery, noradrenaline-induced constriction is conferred by the α1D-subtype (36), so that it is assumed that trophic and contractile effects are at least partially mediated by different receptor subtypes (35). Cell culture experiments identified the trophic signaling pathway to involve generation of reactive oxygen species by nicotinamide adenine dinucleotide phosphate reduced oxidases (37), of which various subtypes are expressed in pulmonary arteries (38, 39), and subsequent transactivation of epidermal growth factor receptor and activation of the mitogen-activated protein kinase/extracellular signal-related kinase 1 and 2 pathway (40).

Although these data provide unequivocal evidence for a significant involvement of catecholamines, still some aspects remain to be solved before distal remodeling effects are finally ascribed as being directly nerve driven, because so far no catecholaminergic axons have been described at this level of the murine pulmonary vascular tree. Alternative sources might be the adrenal medulla and perivascular nerve fibers releasing catecholamines into the circulation or even nonneuronal local cells (e.g., phagocytes) that are known to enhance acute inflammatory lung injury via catecholamine release (41). Thus, additional data, especially on the actual distribution and local activation of noradrenergic axons in the mouse lung, are desirable. In particular, thorough investigations of animals that have been exposed to hypoxia have not been performed. Neurotrophins and their receptors are expressed in cells of the peripheral lung (42), and at least some components of this system are up-regulated by hypoxia (43). Thus, axonal outgrowth might occur under these conditions, and previously noninnervated arterioles might receive innervation. Although quantitative studies have not been performed yet, an early qualitative immunohistochemical study of the pulmonary vasculature in infants and children states that pulmonary hypertension was associated with premature innervation of arteries of the respiratory unit in the first year of life (44).

The common cotransmitter of noradrenaline in pulmonary perivascular axons, NPY, is also a potent stimulator of vascular smooth muscle and endothelial proliferation and an angiogenic factor in systemic vessels (45, 46). Therefore, NPY might be involved in pulmonary vascular remodeling as well, but this issue has not been directly addressed yet. As for noradrenaline, however, studies toward this direction have to take into account nonneuronal sources of NPY, such as endothelial cells (47) and mononuclear blood leukocytes (48).

The classically known parasympathetic pathway to the lung consists of a chain of two cholinergic neurons, the first residing in the nucleus ambiguus in the brainstem and the second in small ganglia situated along the airways and hilar blood vessels (49). The distribution of cholinergic fibers along pulmonary vessels is principally similar to that of noradrenergic fibers, with highest density at large extrapulmonary and hilar vessels and, depending on species, a more or less rapid decrease toward the lung periphery (8, 50, 51). Throughout, however, their density is less than that of noradrenergic axons ( Figure 1 ). Vagal nerve stimulation causes a cholinergic (i.e., atropine sensitive) relaxation of precontracted feline pulmonary arteries, which is NO-dependent (52).

Other transmitters that are also produced by perivascular axons and are usually ascribed to parasympathetic neurons are NO and VIP (7, 44, 53, 54). Both relax precontracted pulmonary arteries with the VIP-induced vasodilation being at least partly dependent on NO (17, 52, 55, 56). The extent of colocalization of acetylcholine, NO, and VIP within perivascular pulmonary nerve fibers is unclear yet. Parasympathetic cholinergic axons also contain VIP and NO synthase (NOS), partly even together with further neuropeptides, at some systemic vessels, such as the guinea pig lingual (57) and uterine arteries (58). The guinea pig trachea, however, is supplied by two separate parasympathetic pathways: a constrictor pathway being cholinergic with cell bodies located in ganglia at the dorsal tracheal surface, and a noncholinergic parasympathetic dilator (!) pathway with NO/VIP-producing nerve cell bodies situated in the esophageal wall (59). Because axons with immunoreactivity to the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT), reach much further distally along the guinea pig pulmonary vasculature than NOS-positive axons (8), there is certainly no 1:1 colocalization of acetylcholine and NOS, if there is any at all. Colocalization of VIP with acetylcholine or NOS yet has not directly been studied in the pulmonary vasculature, but VIP/NPY-positive axons have been detected at large pulmonary arteries of the guinea pig (3). It remains to be determined whether these are parasympathetic nerve fibers or originate from the few noncatecholaminergic sympathetic neurons that can be retrogradely labeled from the lung (3).

Reduced VIP serum and lung tissue levels have been reported in patients with primary arterial hypertension (60), and VIP −/− mice present moderate pulmonary arterial hypertension with up-regulation of proinflammatory and proproliferative genes, perivascular inflammation, increased muscularization, and narrowed lumen of small arteries (61, 62). Although VIP-immunoreactive fibers innervate small muscular pulmonary vessels in the human lung (44), they have not been reported yet at this level in the mouse lung. Therefore, as discussed above for noradrenaline and NPY, it is not clear whether the pulmonary phenotype of VIP −/− mice is due to lack of neuronal VIP or of nonneuronal VIP expressing cells (63).

A subpopulation of unmyelinated, slowly conducting sensory neurons expresses neuropeptides and transports them into the peripheral terminal where they are released on stimulation. Thus, these neurons serve a dual function: (1) conveying information to the central nervous system, and (2) immediately evoking peripheral effects. Such neurons producing peptides derived from the preprotachykinin A gene—substance P (SP), neurokinin A (NKA), and neurokinin B (NKB)—and calcitonin gene-related peptide (CGRP) also innervate pulmonary vessels (3, 17, 44, 64). Depending on species and experimental condition, neurons expressing preprotachykinin A or CGRP have also been observed in airway and pulmonary parasympathetic ganglia (65, 66). Thus, multiple sources of SP- and CGRP-containing pulmonary nerve fibers have to be taken into account. Still, denervation studies in rodents argue for a sensory nature of SP/CGRP-positive perivascular pulmonary axons (64). Such fibers are not numerous at any given level along the pulmonary vascular tree, but reach deep into the lung and are, albeit not frequently, also seen in the parenchyma without obvious relationship to arteries, veins, or airways (3, 64) ( Figure 1 ). In humans, SP content of pulmonary arteries is higher than that of bronchi (67).

These peptides exert markedly different effects on the airway versus the pulmonary vasculature. In the airway mucosa, but not in the lung, stimulation of such peptidergic sensory axons causes a classical “neurogenic inflammation” with plasma leakage from venules (68). All these peptides relax precontracted pulmonary vessels with some peptide-specific profiles on arteries and veins (69–71). The vasodilator response to SP is impaired in patients with pulmonary hypertension (72).

Peptidergic sensory nerve fibers do not play a clear role in modulating hypoxic pulmonary vasoconstriction (73). As for the other neurotransmitters found in perivascular axons, however, there is evidence for an involvement in pulmonary vascular remodeling. Rats treated with a stable analog of SP develop pulmonary hypertension with thickening of the arterial media, which can be prevent by a tachykinin NK-1 receptor antagonist (74). Again, it remains to be resolved whether respective nerve fibers in situ can play a role in the pathogenesis of pulmonary vascular remodeling.

Sympathetic pulmonary vascular neurons are reflexively activated via arterial chemoreceptors when arterial P o 2 is lowered and adapt the pulmonary vasculature to this condition of increased pulmonary blood flow by α1-adrenoreceptor–mediated increase in vascular resistance and, more pronounced, stiffness. Terminating primarily at large vessels, these fibers have impact on pulmonary vascular input impedance and pulmonary arterial capacitance, which are closely coupled to the clinical outcome in patients with pulmonary hypertension. Nerve fibers are not responsible, however, for the local hypoxic vasoconstriction triggered by low alveolar P o 2, which serves to match perfusion to ventilation. Instead, a major potential role of the pulmonary vascular innervation, autonomic and sensory, lies in the pronounced trophic activities of its transmitters. To further elucidate this potential, in-depth investigation of coutilization of trophically active transmitters by neuronal subpopulations and of plastic changes in transmitter phenotype and innervation pattern of remodeling vessels are required.


The cardiac plexus

The cardiac plexus is a network of nerves including both the sympathetic and parasympathetic systems. It is split into two parts. The superficial part is located below the arch of the aorta, and between the arch and the pulmonary trunk.

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The deep part lies between the arch of the aorta and the bifurcation of the trachea. Small mixed fibres (containing both sympathetic and parasympathetic fibres) branch off of the cardiac plexus and supply:

Parasympathetic innervation

The parasympathetic portions of the cardiac plexus receive contributions from the vagus nerve only. The preganglionic fibres, branching from the right and left vagus nerves, reach the heart. They enter the cardiac plexus by synapsing with ganglia within this plexus and walls of the atria.

Parasympathetic innervation is responsible for:

  • reducing the heart rate
  • reducing the force of contraction of the heart
  • vasoconstriction (narrowing) of the coronary arteries

Sympathetic innervation

The sympathetic part of the cardiac plexus is composed of fibres from the sympathetic trunk, arising from the upper segments of the thoracic spinal cord. Fibres from the sympathetic trunk reach the cardiac plexus via cardiac nerves. The preganglionic fibres branch from the upper thoracic spinal cord and synapse in the lower cervical and upper thoracic ganglia. Postganglionic fibres extend from the ganglia to the cardiac plexus.

Sympathetic nerves are responsible for:

  • increasing heart rate
  • increasing the force of contraction of the myocardium
  • the ‘fight or flight’ response, causing our heart to beat faster.

Cardiac afferents

Afferent fibres also form part of the cardiac plexus. They return to the central nervous system via both the sympathetic cardiac branches and the cardiac nerves from the right and left vagus nerves.

The afferents passing through the vagal cardiac nerves return to the corresponding vagus nerve. These afferents provide feedback on blood pressure and blood chemistry.

In the sympathetic branch, the visceral afferents return to the upper thoracic and lower cervical ganglia. The fibres entering the upper cervical region are typically redirected down towards the upper thoracic portions of the sympathetic trunk, where they reenter the upper thoracic regions of the thoracic spinal cord, joining afferents from the thoracic ganglia. Sympathetic afferents relay pain sensation from the heart.

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Vasoconstriction

Physical activity such as exercise stimulates the sympathetic nervous system to constrict blood vessels to increase blood pressure and speed up blood flow, according to McGrawHillEducation.com. This happens to meet the body’s increased need for oxygen. Blood vessels around the skin and visceral organs constrict as blood is redirected to the muscles in order to sustain physical activity. However, as body temperature increases later in the exercise, this stimulates vasoconstriction to decrease and reverse.


AUTONOMIC NERVOUS SYSTEM

The autonomic nervous system (ANS) is the component of the peripheral nervous system that controls cardiac muscle contraction, visceral activities, and glandular functions of the body. Specifically the ANS can regulate heart rate, blood pressure, rate of respiration, body temperature, sweating, gastrointestinal motility and secretion, as well as other visceral activities that maintain homeostasis[1-4]. The ANS functions continuously without conscious effort. The ANS, however, is controlled by centers located in the spinal cord, brain stem, and hypothalamus.

The ANS has two interacting systems: the sympathetic and parasympathetic systems. As illustrated in Figure ​ Figure1, 1 , sympathetic and parasympathetic neurons exert antagonistic effects on the heart. The sympathetic system prepares the body for energy expenditure, emergency or stressful situations, i.e., fight or flight. Conversely, the parasympathetic system is most active under restful conditions. The parasympathetic counteracts the sympathetic system after a stressful event and restores the body to a restful state. The sympathetic nervous system releases norepinephrine (NE) while the parasympathetic nervous system releases acetylcholine (ACh). Sympathetic stimulation increases heart rate and myocardial contractility. During exercise, emotional excitement, or under various pathological conditions (e.g., heart failure)[5], the sympathetic nervous system is activated. The stimulation of the sympathetic nervous system causes pupil dilatation, bronchiole dilatation, blood vessel constriction, sweat secretion, inhibits peristalsis, increases renin secretion by the kidneys, as well as can induce reproductive organ contraction and secretion. In contrast, parasympathetic stimulation decreases heart rate and constricts the pupils. It also increases secretion of the eye glands, increases peristalsis, increases secretion of salivary and pancreatic glands, and constricts bronchioles. Most organs receive innervations from both systems, which usually exert opposing actions. However, this is not always the case. Some systems do not have a response to parasympathetic stimulation. For example, most blood vessels lack parasympathetic innervations and their diameter is regulated by sympathetic nervous system input, so that they have a constant state of sympathetic tone. It is a decrease in sympathetic stimulation or tone that allows vasodilatation. During rest, sleep, or emotional tranquility, the parasympathetic nervous system predominates and controls the heart rate at a resting rate of 60-75 bpm. At any given time, the effect of the ANS on the heart is the net balance between the opposing actions of the sympathetic and parasympathetic systems.

Autonomic nervous system regulation of the heart function. The autonomic nervous system affects the rate and force of heart contractions. CNS: Central nervous system RA: Right atria LA: Left atria RV: Right ventricle LV: Left ventricle SA: Sino-atrial node AV: Atrioventricular node NE: Norepinephrine ACh: Acetylcholine.

Unlike the somatic nervous system, where a single neuron originating in the spinal cord typically connects the central nervous system and a skeletal muscle via a neuromuscular junction, both sympathetic and parasympathetic pathways are composed of a two-neuron chain: a preganglionic neuron and a postganglionic neuron. The neurotransmitter between the preganglionic and postganglionic neurons is acetylcholine, the same as that in neuromuscular junctions. Messages from these systems are conveyed as electrical impulses that travel along axons and cross synaptic clefts (using chemical neurotransmitter).

In the sympathetic system (thoracolumbar division), these nerves originate from the thoracolumbar region of the spinal cord (T1-L2) and radiate out towards the target organs. In contrast, the nerves of the parasympathetic system originate within the midbrain, pons and medulla oblongata of the brain stem and part of these fibers originate in the sacral region (S2-S4 sacral spinal nerves) of the spinal cord. While sympathetic nerves utilize a short preganglionic neuron followed by a relatively long postganglionic neuron, parasympathetic nerves (e.g., the vagus nerve, which carries about 75 percent of all parasympathetic fibers) have a much longer preganglionic neuron, followed by a short postganglionic neuron.

Cardiac sympathetic nervous system

The sympathetic nervous system is the component of the ANS that is responsible for controlling the human body’s reaction to situations of stress or emergency (otherwise known as the 𠇏ight-or-flight” response), while the parasympathetic nervous system is generally responsible for basal organ system function.

Cardiac sympathetic preganglionic nerves (typically all myelinated) emerge from the upper thoracic segments of the spinal cord (T1-T4). After traveling a short distance, preganglionic fibers leave the spinal nerves through branches called white rami and enter sympathetic ganglia. The cardiac sympathetic neurons form the sympathetic chain ganglia located along the side of the viscera column (i.e., paravertebral ganglia). These ganglia comprise the sympatheric trunks with their connecting fibers. The postganglionic fibers, extend to the viscera, such as the heart. In general, sympathetic preganglionic neurons are shorter than sympathetic postganglionic neurons (Figure ​ (Figure1 1 ).

Sympathetic neurotransmitters: Neurotransmitters are chemical substances released into the synaptic cleft from nerve terminals in response to action potentials. They transmit signals from a neuron to a target cell across a synapse, e.g., acetylcholine for neuromuscular junctions. While the preganglionic neurons of both the sympathetic and parasympathetic system secret acetylcholine (ACh) which is why they are referred to as cholinergic, the majority of the postganglionic endings of the sympathetic nervous system release NE, which resembles epinephrine (i.e., adrenalin). Thus, these sympathetic postganglionic fibers are commonly called adrenergic fibers.

Sympathetic receptors: There are two types of adrenergic receptors: β and α. In the cardiovascular system there are β1, β2, α1, and α2 adrenergic receptors (Table ​ (Table1 1 ).

Table 1

Sympathetic and parasympathetic receptors and their functions in the heart and vessels

HeartVessels
ReceptorFunctionReceptorFunction
InotropyChronotropyDromotropy
Norepinephrineα1+++α1Vasoconstriction
β1+++β1Vasoconstriction
β2+++β2Vasodilation
AcetylcholineM2---M2Vasodilation

β1 adrenergic receptors are expressed in the heart (in the SA node, AV node, and on atrial and ventricular cardiomyocytes). The activation of β1 receptors increases heart rate (via the SA node), increases contractility as result of increased intracellular calcium concentrations and increased calcium release by the sarcoplasmic reticulum (SR), and increased AV node conduction velocity. Additionally, activation of this receptor also induces renin release by the kidneys to help maintain blood pressure, plasma sodium levels and blood volume.

β2 adrenergic receptors are mainly expressed in vascular smooth muscle, skeletal muscle, and in the coronary circulation. Their activation elicits vasodilatation, which, in turn increases blood perfusion to target organs (especially the liver, heart, and skeletal muscle). These receptors are not innervated and thus are primarily stimulated by circulating epinephrine. There are also some low expressions of β2 receptors in cardiomyocytes.

α1 adrenergic receptors are expressed in vascular smooth muscle proximal to sympathetic nerve terminals. Their activation elicits vasoconstriction. There are also some low expressions of α1 receptors in cardiomyocytes.

α2 adrenergic receptors are expressed in vascular smooth muscle distal from sympathetic nerve terminals. Their activation also elicits vasoconstriction.

Sympathetic nervous system control and heart function: Stimulation by the sympathetic nervous system results in the following effects on the heart (Table ​ (Table1): 1 ): Positive chronotropic effect (increase in heart rate): The sinoatrial (SA) node is the predominate pacemaker of the heart. It is located within the upper posterior wall of the right atrium, and is responsible for maintaining a sinus rhythm of between 60 and 100 beats per minute. This rate is constantly being affected by innervations from both the sympathetic and parasympathetic nervous systems. Stimulation by the sympathetic system nerves results in an increase of heart rate, as occurs during the 𠇏ight-or-flight” response.

Positive inotropic effect (increase of contractility): Myocardial contractility represents the ability of the heart to produce force during contraction. It is determined by the incremental degrees of binding between myosin (thick) and actin (thin) filaments, which in turn depends on the concentration of calcium ions (Ca 2+ ) in the cytosol of the cardiomyocyte. Stimulation by the sympathetic nervous system causes an elevation in intracellular (Ca 2+ ) and thus an increase in contraction of both the atria and ventricles.

Positive dromotropic effect (enhancement of conduction): Stimulation by the sympathetic nervous system also enhances the conductivity of the electrical signal. For example, it increases AV conduction velocity.

Parasympathetic nervous system

As previously mentioned, the parasympathetic nervous system is responsible for the unconscious regulation of the body’s systems, most notably, salivation, lacrimation, urination, digestion, and defecation (acronym SLUDD). Importantly, the parasympathetic nervous system plays an antagonistic role in regulating heart function.

The parasympathetic system has preganglionic neurons (craniosacral division) that arise from neurons in the mid-brain, pons and medulla oblongata. The cell bodies of parasympathetic preganglionic neurons are located in the homologous motor nuclei of the cranial nerves. Parasympathetic preganglionic fibers associated with parts of the head are carried by the oculomotor, facial, and glossopharygeal nerves. The fibers that innervate organs of the thorax and upper abdomen are parts of the vagus nerve which as previously mentioned carries approximately 75% of all parasympathetic nerve fibers passing to the heart, the lungs, the stomach, and many other visceral organs. Preganglionic fibers arising from the sacral region of the spinal cord make up parts of S2-S4 sacral spinal nerves and carry impulses to viscera in the pelvic cavity. The short postganglionic neurons reside near effector organs, e.g., lacrimal gland, salivary glands, heart, trachea, lung, liver, gallbladder, spleen, pancreas, intestines, kidney, and urinary bladder, etc. Unlike the sympathetic system, most parasympathetic preganglionic fibers reach the target organs and form the peripheral ganglia in the wall of the organ. The preganglionic fibers synapse within the ganglion, and then short postganglionic fibers leave the ganglia to the target organ. Thus, in the parasympathetic system, preganglionic neurons are generally longer than postganglionic neurons (Figure ​ (Figure1 1 ).

Parasympathetic neurotransmitters: Acetylcholine is the predominant neurotransmitter from the parasympathetic nervous system, in both the preganglionic and postganglionic neurons. Although excitatory in skeletal muscle by binding to nicotinic receptors and inducing the opening of ligand gated sodium channels, acetylcholine inhibits the contraction of cardiomyocytes by activating muscarinic receptors (M2). These parasympathetic postganglionic fibers are commonly called cholinergic fibers because they secrete acetylcholine at their nerve endings.

Acetylcholine is synthesized by choline acetlytransferase in cholinergic neurons by combining choline and acetyl-COA molecules. Once assembled in synaptic vesicles near the end of the axon, the entry of calcium causes the vesicles to fuse with the membrane of the neuron and to release acetylcholine into the synaptic cleft (the space between the neuron and post-synaptic membrane or effector cell). Acetylcholine diffuses across the synaptic cleft and binds to receptors on the post-synaptic membrane increasing the permeability to sodium causing depolarization of the membrane and propagation of the impulse. This chemical transmission is much slower than the electrical 𠇊ll or none” transmission of the action potential seen in the intrinsic nervous system of the heart. To regulate the function of these neurons (and thus, the muscles they control), acetylcholinesterase is present in the synaptic cleft. It serves to hydrolyze the acetylcholine molecule by breaking it down into choline and acetate, which are then both taken back up by the neuron, to be again synthesized into acetylcholine.

Parasympathetic receptors: The parasympathetic postganglionic fibers are cholinergic. Acetylcholine can bind to two types of cholinergic receptors called nicotinic receptors and muscarinic receptors. Muscarinic receptors are located in the membranes of effector cells at the end of postganglionic parasympathetic nerves and at the ends of cholinergic sympathetic fibers. Responses from these receptors are excitatory and relatively slow. The nicotinic receptors are located at synapses between pre- and post-ganglionic neurons of the sympathetic and parasympathetic pathways. Nicotinic receptors in contrast to muscarinic receptors produce rapid, excitatory responses. Neuromuscular junctions found in skeletal muscle fibers are nicotinic.

In relation to the cardiovascular system the parasympathetic nervous system has two different kinds of muscarinic receptors: the M2 and M3 receptors (Table ​ (Table1 1 ).

The M2 receptors are expressed in the heart abundant in nodal and atrial tissue, but sparse in the ventricles. The binding of acetylcholine to M2 receptors serves to slow heart rate till it reaches normal sinus rhythm. This is achieved by slowing the rate of depolarization, as well as by reducing the conduction velocity through the atrioventricular node. Additionally, the activation of M2 receptors reduces the contractility of atrial cardiomyocytes, thus reducing, in part, the overall cardiac output of the heart as a result of reduced atrial kick, smaller stroke volume, and slower heart rate. Cardiac output is determined by heart rate and stroke volume (CO = HR x SV).

The M3 receptors are mainly expressed in vascular endothelium. The predominate effect of M3 receptor activation is dilatation of the vessels, by stimulating nitric oxide production by vascular endothelial cells[6]. M3 receptors impact afterload and vascular resistance which can again alter cardiac output and blood pressure.

Parasympathetic nervous system control and heart function: As mentioned earlier, parasympathetic activity produces effects that are, in general, opposite to those of sympathetic activation. However, in contrast to sympathetic activity, the parasympathetic nervous system has little effect on myocardial contractility.

Negative chronotropic effect (decrease in heart rate): The vagus nerve directly innervates the sinoatrial node when activated, it serves to lower the heart rate, thus exhibiting a negative chronotropic effect.

Negative inotropic effect (decrease in myocardial contractility): Currently, it is a matter of debate whether parasympathetic stimulation can exhibit negative inotropic effects, as the vagus nerve does not directly innervate cardiomyocytes other than that of the sinoatrial and atrioventricular nodes, however, recent in vivo studies may suggest otherwise, at least in the atrium.

Negative dromotropic effect (decrease conduction velocity): Stimulation of the parasympathetic system serves to inhibit AV node conduction velocity.

Cellular signal transduction

Most sympathetic and parasympathetic receptors are known to be G protein-coupled receptors (GPCRs). In the heart, the G-protein-cAMP-PKA signaling pathway mediates the catecholaminergic control on heart rate and contractility.

Signaling pathway of sympathetic stimulation: The sympathetic stimulation-induced effects in the heart result from activation of β1-adrenoceptors, which are GPCRs (Figure ​ (Figure2). 2 ). The sympathetic neurotransmitter NE (as well as other catecholamines) bind to β1 receptors and activate stimulatory G proteins (Gs) by causing a conformational change within the Gs, so that the disassociated αs subunit can then bind to and activate adenylyl cyclase (AC). The activation of this enzyme then catalyzes the conversion of ATP into cyclic adenosine monophosphate (cAMP). This second messenger may then activate a myriad of other pathways, ion channels, transcription factors, or enzymes. With regards to the cardiovascular system, the most important enzyme that cAMP activates is protein kinase A (PKA). PKA, which in turn, phosphorylates multiple target proteins, such as L-type Ca channels (LTCC), the SR Ca handling protein phospholamban, and contractile machinery such as troponin C, I and T. Additionally, cAMP binds directly to ion channels responsible for the funny current (If), thus increasing the heart rate[7].

Signal transduction systems for β-adrenergic receptor and muscarinic-receptor stimulations in a cardiac myocyte. NE: Norepinephrine 㬡: Beta1-adrenergic receptor Gs: Stimulatory G-protein: Ach: Acetylcholine m2: Type-2 muscarinic receptors Gi: Inhibitory G-protein AC: Adenylate cyclase PKA: Protein kinase A ICa,L: L-type Ca channel RyR2: Ryanodine receptor 2 SERCA: Sarcoplasmic reticulum Ca 2+ -ATPase2a PLB: Phospholamban.

Signaling pathway of parasympathetic stimulation: The parasympathetic stimulation-induced effects in the heart result from activation of muscarinic (M2) receptors, which are also GPCRs by acetylcholine (Figure ​ (Figure2). 2 ). The parasympathetic neurotransmitter ACh binds to M2 receptors thereby activating inhibitory G proteins (Gi) by causing a conformational change within the Gi subunit, so that the disassociated αi subunit can then bind to and inhibits AC. Since M2 receptors are negatively coupled to AC and thus reduce cAMP formation, M2 receptors act to inhibit PKA activity and exert an opposite effect on ion channels, Ca 2+ handling proteins, and contractile machinery, compared to sympathetic stimulation.

Autorhythmic cells: Regulation of pacemaking current and heart rate: The funny current (If) is thought to be the pace making current in the SA node. It is a non-selective cation channel that can inwardly conduct both sodium and potassium ions. As the membrane potential becomes increasingly hyperpolarized during phase 3 and 4 of the action potential, If increases inward potassium and sodium currents, which causes the phase 4 diastolic depolarization. If channels are activated by direct binding of cAMP[7].

In addition to the funny current, one of the other driving mechanisms behind the automaticity of the pacemaking cells within the SA node is the calcium clock[8]. As the SR fills with calcium, the probability of spontaneous calcium release increases in contrast, when the SR calcium stores are depleted, the probability of spontaneous calcium release is reduced. Increased Ca 2+ entry also increases automaticity because of the effect of [Ca 2+ ]i on the transient inward current carried by the sodium-calcium exchange current (INCX). When these pacemaking mechanisms depolarize the resting membrane potential and reach the threshold voltage, which induces the opening of L-type Ca channel (LTCC), an action potential is fired.

On the other hand, M2 receptor stimulation opens muscarinic potassium channels (KACh)[9]. These channels are opened by M2 receptors binding to ACh and produce a hyperpolarizing current that opposes the inward pacemaker current. Therefore, the parasympathetic stimulation increases outward K + permeability, slowing the heart rate and reducing automaticity.

Cardiomyocytes: Regulation of cellular Ca 2+ handling and cardiac contraction: Excitation-contraction coupling in cardiomyocytes is dependent on calcium-induced calcium release, whereby an action potential initiates an increase in cellular calcium through opening of the LTCC on the cellular membrane. This creates a positive feedback loop by activating the ryanodine receptors of the SR causing the release of an even greater amount of calcium. This calcium then binds to troponin C, moving the tropomyosin complex off the actin active site, so that the myosin head can bind to the actin filament. Hydrolysis of ATP then causes the myosin head to pull the actin filament toward the center of the sarcomere. Free intracellular calcium is then resequestered into the SR via the SR ATPase pump (SERCA), or is pumped from the cell via the sodium-calcium exchanger on the cellular membrane. Finally, the troponin complex returns the actin filament to its binding sites to tropomyosin.

Sympathetic stimulation leads to the elevation of cAMP levels and the activation of PKA, which phosphorylates the α1 subunits of the LTCCs. This increases the opening probability of LTCCs and the inward Ca 2+ current, and thus enhances the force of cardiac contraction. In addition, PKA phosphorylates phospholamban, thus relieving its inhibition of SERCA, which in turn facilitates Ca 2+ uptake by the SR and increases the amount of Ca 2+ (i.e., SR Ca 2+ content) available for release by the action potential. Furthermore, activation of β1-adrenoceptors also increases the Ca 2+ sensitivity of the contractile machinery, mediated by phosphorylation of troponin C. Taken together, the net result of sympathetic stimulation is to elevate cardiac function and steepen both contraction and relaxation.

Since M2 receptors are negatively coupled to AC and thus reduce cAMP formation, they act to decrease the open probability of LTCCs and reduce Ca 2+ current. In opposition to sympathetic stimulation, parasympathetic stimulation reduces the activity of Ca 2+ handling proteins in cardiomyocytes.

Autonomic regulation of vascular function: In contrast to the heart, most vessels (arteries and veins) only receive sympathetic innervation, while capillaries receive no innervation. These sympathetic nerve fibers tonically release norepinephrine, which activates α1-adrenergic and β2-adrenergic receptors on blood vessels thereby providing basal vascular tone. Since there is greater α1-adrenergic than β2-adrenergic receptor distribution in the arteries, activation of sympathetic nerves causes vasoconstriction and increases the systemic vascular resistance primarily via α1 receptor activation. On the other hand, modified sympathetic nerve endings in the adrenal medulla release circulating epinephrine, which also binds to α1 and β2-adrenergic receptors in vessels. However, β-adrenergic receptors show greater affinity for epinephrine than for norepinephrine. Therefore, circulating epinephrine at low concentrations activates only β1-adrenergic (mainly in the heart) and β2-adrenergic (mainly in vessels) receptors, which increase cardiac output and cause vasodilation, respectively. It should be noted that vessels at different locations may react differently to sympathetic stimulation. For example, during the 𠇏ight or flight” response the sympathetic nervous system causes vasodilation in skeletal muscle, but vasoconstriction in the skin.

Cardiovascular reflexes and the regulation of blood pressure

In the human body, the ANS is organized as functional reflex arcs (Figure ​ (Figure3). 3 ). Sensory signals from receptors distributed in certain parts of the body are relayed via afferent autonomic pathways to the central nervous system (i.e., spinal cord, brain stem, or hypothalamus), the impulses are then integrated and transmitted via efferent pathways to the visceral organs to control their activities. The following reflexes play major roles in regulating cardiovascular functions.

Schematic of cardiovascular reflexes and their influences on heart and vessels functions. NTS: Nucleus tractussolitarii Symp: Sympathetic CNS: Central nervous system RAAS: Renin-angiotensin-aldosterone system.

Baroreceptor reflex: Baroreceptors located within the aortic arch and the carotid sinuses detect increases in blood pressure. These mechanoreceptors are activated when distended, and subsequently send action potentials to the rostral ventrolateral medulla (RVLM located in the medulla oblongata of the brainstem) which further propagates signals, through the autonomic nervous system, adjusting total peripheral resistance through vasodilatation (sympathetic inhibition), and reducing cardiac output through negative inotropic and chronotropic regulation of the heart (parasympathetic activation). Conversely, baroreceptors within the venae cavae and pulmonary veins are activated when blood pressure drops. This feedback results in the release of antidiuretic hormone from cell bodies in the hypothalamus into the bloodstream from the nerve endings in the posterior lobe of the pituitary gland. The renin-angiotensin-aldosterone system is also activated. The subsequent increase in blood plasma volume then results in increased blood pressure. The final baroreceptor reflex involves the stretch receptors located within the atria like the mechanoreceptors in the aortic arch and carotid sinuses, the receptors are activated when distended (as the atria become filled with blood), however, unlike the other mechanoreceptors, upon activation, the receptors in the atria increase the heart rate through increased sympathetic activation (first to the medulla, then subsequently to the SA node), thus increasing cardiac output and alleviating the increased blood volume-caused pressure in the atria[10].

Chemoreceptor reflex: Peripheral chemoreceptors located in the carotid and aortic bodies monitor oxygen and carbon dioxide content as well as the pH of the blood. Central chemoreceptors are located on the ventrolateral medullary surface in the central nervous system and are sensitive to the surrounding pH and CO2 levels. During hypovolemia or severe blood loss, blood oxygen content drops and/or pH is decreased (more acidic), and levels of carbon dioxide are likely increased, action potentials are sent along the glossopharyngeal or vagus nerves (the former for the carotid receptors, the latter for the aortic) to the medullary center, where parasympathetic stimulation is decreased, resulting in an increase in heart rate (and thus an increase in gas exchange as well as respiration). Additionally, sympathetic stimulation is increased, resulting in further increases to heart rate, as well as stroke volume, which in turn results in an even greater restoration of cardiac output.

Cardiovascular autonomic dysfunction and heart rate variability: It has been known that sympathetic stress/dominance occurs during heart failure or after myocardial infarction, and may trigger lethal arrhythmias. This sympathovagal imbalance is reflected by reduced heart rate variability (HRV). HRV is determined from ECG and has currently been used clinically as both a diagnostic as well as a prognostic factor for assessing cardiovascular autonomic dysfunction including cardiac autonomic neuropathy. Please refer a recent review article for specific HRV indicators and their interpretations[11].


Contents: Difference between Parasympathetic and Sympathetic Nervous System

Comparison Chart

Basis Parasympathetic Nervous System Sympathetic Nervous System
Definition It is a part of the autonomic nervous system that controls the functions of the body at rest It is a part of the autonomic nervous system that prepares the body during fight or flight response
Function It causes muscles to relax and heart rate to decrease and also involved in maintaining homeostasis in the body It causes muscles to contract and heart rate to increase and prepare the body for intense physical activity
Response Time Due to the longer neuronal pathway, it has a slower response time It gives comparatively quicker response due to shorter neuronal pathway
Ganglion Location Ganglions of the parasympathetic nervous system are found away from the central nervous system but close to the effector. Ganglions are found close to the central nervous system but away from the effector
Size of Pre-Ganglionic Fibers Long Short
Size of Post-Ganglionic Fibers Short Long
Numbers of Post-Ganglionic Fibers A small number of post-ganglionic fibers are found in the parasympathetic nervous system Large number of post-ganglionic fibers are found in the sympathetic nervous system
Neurotransmitter Released Acetylcholine released at the effector to produce a cholinergic response Nor adrenaline released at the effector
Effect on Metabolic Rate Decreases metabolic rate Increases metabolic rate
Effect on Heart Rate Decrease Increase
Effect on Saliva Secretion It stimulates saliva secretions Saliva secretion is inhibited
Effect on Pupil Constricts pupil Dilates pupil
Effect on Urinary Output Increases the urinary output and relaxes the rectum Decreases the urinary output and constricts the rectum
Effect on Adrenaline Gland It has no action on the adrenaline gland Stimulates the production of adrenaline from the adrenal gland
Effect on Pulmonary System Constricts bronchial tubes Dilates bronchial tubes
Effect on Target Area Parasympathetic nervous system generates a localized effect at the target area It generates a diffused effect at its target area

What is Parasympathetic Nervous System?

The parasympathetic nervous system is one of the three divisions of the autonomic nervous system which is sometimes also called as, “The Rest & Digest System”.

It is generally involved in controlling the unconscious actions of the body such as digestion, respiration, and heart rate when the body is feeding, resting, or relaxed. It basically undoes the work of Sympathetic Nervous System.

For example, during a fight and flight response, (during stress or injury) the Sympathetic Nervous System performs the following functions,

  • Inhibits digestion.
  • Constricts blood vessels and diverts blood flow away from the gastrointestinal (GI) tract and skin
  • Blood flow to skeletal muscles and the lungs is enhanced (by as much as 1,200% in the case of skeletal muscles).
  • Dilates bronchioles of the lung, which allows for greater alveolar oxygen exchange at rest.
  • Increases heart rate and the contractility of cardiac cells (myocytes), thereby providing a mechanism for the enhanced blood flow to skeletal muscles.
  • Dilates pupils and relaxes the ciliary muscle by allowing more light to enter the eye and far vision.
  • Enhance vasodilation for the coronary vessels of the heart.
  • Constricts all the intestinal sphincters and the urinary sphincter.
  • Inhibits peristalsis.
  • Stimulates orgasm.

Conversely, the parasympathetic nervous system is involved to bring the body back into homeostasis to conserve precious energy and do the following functions,

  • Dilates blood vessels connecting to the GI tract and increasing blood flow.
  • It constricts the bronchioles when the need for oxygen has reduced.
  • It causes constriction of the pupil and contraction of the ciliary muscle.
  • Stimulates salivary gland secretion, and accelerates peristalsis.
  • Stimulates sexual arousal.

What is Sympathetic Nervous System?

Another division of the autonomic nervous system is the sympathetic nervous system which is especially known for its “fight-or-flight” response.

The sympathetic nervous system prepares your body to either run from danger or fight back. It’s also activated in response to mental or physical stress. During the fight-or-flight response, the following occurs:

  • Blood pressure increases
  • Blood flow increases to muscles, lungs, and other areas essential for moving away from perceived danger
  • Blood flow decreases to the digestive and reproductive systems
  • Stress hormones, such as cortisol, and neurotransmitters, like epinephrine, increase to make us stronger and faster
  • Glucose is rapidly released to be burned for quick energy

The SNS is perhaps best known for mediating the neuronal and hormonal stress response commonly known as the fight-or-flight response, also known as sympathoadrenal response of the body. This occurs as the preganglionic sympathetic fibers that end in the adrenal medulla secrete acetylcholine, which activates the secretion of adrenaline (epinephrine), and to a lesser extent nor adrenaline (nor epinephrine).

Therefore, this response is mediated directly via impulses transmitted through the sympathetic nervous system, and also indirectly via catecholamines that are secreted from the adrenal medulla, and acts primarily on the cardiovascular system.

Messages travel through the sympathetic nervous system in a bidirectional flow. Efferent messages can trigger simultaneous changes in different parts of the body.

For example, the sympathetic nervous system can accelerate heart rate, widen bronchial passages, decrease motility of the large intestine, constrict blood vessels, increase peristalsis in the esophagus, cause pupillary dilation, piloerection (goosebumps) and perspiration (sweating), and raise blood pressure.

Some evolutionary theorists suggest that the sympathetic nervous system operated in early organisms to maintain survival since the sympathetic nervous system is responsible for priming the body for action. One example of this priming is in the moments before waking, in which sympathetic outflow spontaneously increases in preparation for activity.

Key Differences between Parasympathetic and Sympathetic Nervous System

  1. The parasympathetic nervous system restores the body to a calm and composed state and prevents it from overworking whereas the sympathetic nervous system prepares the body for fight and flight response.
  2. The sympathetic nervous system releases the hormones epinephrine and nor epinephrine that accelerate the heart rate while the parasympathetic nervous system releases acetylcholine, the hormone that slows down the heart rate.
  3. The parasympathetic nervous system is composed of cranial and spinal nerves. The sympathetic nervous system comprises cell bodies that lie within the gray column of the spinal cord.

Comparison Video

Conclusion

The autonomic nervous system comprises of two parts- the sympathetic and parasympathetic nervous system. The sympathetic nervous system activates the fight or flight response during a threat or perceived danger, and the parasympathetic nervous system restores the body to a state of calm.


Using these nervous systems to your benefit

The less time we spend in the sympathetic response mode, the better. Although it makes us alert and better able to respond to the challenges ahead, it takes a huge toll on our bodies after a while and can lead to adrenal fatigue. Anything we can do to keep ourselves in the “rest and digest” mode as much as possible is worth the effort, since our long-term health may depend on it.

To activate your parasympathetic nervous system, learn what truly makes you feel relaxed. For some, this means engaging in a hobby, hanging out with friends, doing some light exercise, or even just getting out into nature. Others find that techniques like yoga, deep breathing, meditation or massage help. My Adrenal Fatigue Solution ebook contains lots of advice on many of these techniques. Whatever it is, pay close attention to your feelings and thoughts, and try to recreate that mental and emotional state whenever you are under stress.

We are all under some level of chronic stress these days. By learning to activate your parasympathetic nervous system, and reducing the effect of your sympathetic nervous system, you can reduce the stress on your heart, digestive system, immune system and more. This will not only make you a happier person, it will also help to avoid many of the diseases and conditions that are associated with chronic stress and adrenal fatigue. If you can become more conscious of the way that your body reacts to stress, it will pay enormous dividends in the future.

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Do you find yourself constantly fatigued, and struggling to get out of bed in the mornings? Do you feel unable to cope with stressful situations? If so, you might be suffering from Adrenal Fatigue Syndrome.


Watch the video: ZAVŘETE OČI, ODCHÁZÍM.. Proč se stahuju z pódia. Aktuálně. (August 2022).