This document summarizes the regulation of the cardiovascular system by the autonomic nervous system. It discusses how the sympathetic and parasympathetic nervous systems control heart rate and contractility through positive and negative chronotropic and inotropic effects. The parasympathetic nervous system acts through the vagus nerve to slow the heart rate, while the sympathetic nervous system increases heart rate. Both divisions also affect blood vessel diameter and peripheral blood flow through vasoconstriction and vasodilation. Local metabolic factors also contribute to regulation of blood flow through autoregulation in tissues.

1. CARDIO- VASCULAR SYSTEM: REGULATION

2. EXTRINSIC CARDIAC MECHANISMS Cardiac output must be variable to meet the changing needs of the body. It is determined by two factors: 1. heart rate (HR) which is determined by the frequency with which the SA node reaches threshold (slope of the pacemaker potential) 2. stroke volume (SV) which is determined by the difference between the end diastolic volume (EDV) and the end systolic volume (ESV): SV = EDV - ESV An increase in heart rate or stroke volume will increase cardiac output and an increase in both will have an additive effect, increasing it even more.

3. CONTROL OF HEART RATE Heart rate is normally controlled by the Autonomic Nervous System (ANS), and under normal resting conditions the heart beats at about 72/min. During sleep this falls by 10 to 20 beats and during exercise may increase by 2 to 3 times .

4. CARDIAC OUTPUT & DIVISIONS OF THE ANS Nervous input to the heart is received from both sympathetic and parasympathetic divisions of the ANS. In humans, parasympathetic tone predominates, meaning that the resting heart rate is slower than it would be if the heart was denervated.

5. PARASYMPATHETIC ACTIVATION Parasympathetic impulses reach the heart via preganglionic fibers in the Vagus Nerve. The right Vagus supplies primarily the SA node and atrial muscle. The left Vagus supplies primarily the AV node and some ventricular muscle. Some of the Vagal fibers also synapse on sympathetic postganglionic terminals and reduce the amount of transmitter released by sympathetic activation.

6. PARASYMPATHETIC ACTIVATION Stimulation of the right Vagus has a pronounced effect on heart rate, causing it to slow. Strong Vagal stimulation may stop the heart (Vagal arrest). Stimulation of the left Vagus slows or blocks conduction in the AV node. However, there is considerable overlap.

7. VAGAL EFFECTS The effect of parasympathetic stimulation is mediated via increased K + permeability and the effect is described as a negative chronotropic effect . Vagal stimulation has two distinct effects on the heart. It causes the slope of the pacemaker potential to decrease and also causes hyperpolarization of pacemaker cells .

8. VAGAL EFFECTS Stimulation of the Vagus nerve causes a negative inotropic effect that includes: A shift of the ventricular function curve to the right Reduced peak systolic pressure Reduced rate of contraction and relaxation

9. SYMPATHETIC ACTIVATION Sympathetic efferent fibers originate in segments C 5 to T 7 of the cord, and short preganglionic fibers enter paravertebral ganglia, where they synapse and send long postganglionic fibers to the heart. Stimulation of these cardiac sympathetic efferent fibers on the right side has a predominant effect on rate (a positive chronotropic effect ). Stimulation of fibers on the left influences contractility, or contractile force (a positive inotropic effect ). As with parasympathetic fibers, there is considerable overlap.

10. SYMPATHETIC EFFECTS Stimulation of sympathetic fibers increases the rate of depolarization of pacemaker cells (by increasing permeability to sodium, potassium, and calcium) and also increases conduction velocity of action potentials through the AV node. There is no effect on the resting membrane potential.

12. SYMPATHETIC EFFECTS Stimulation of sympathetic postganglionic fibers elicits a positive inotropic effect that has the following results: Shifts the ventricular function curve to the left Increases peak systolic pressure Increases the rate of pressure development Increases the rate of relaxation Shortens the duration of systole

13. FACTORS INFLUENCE HEART RATE Changes in plasma ion concentration (especially K + ), circulating hormone levels (thyroxin, epinephrine and norepinephrine), body temperature (fever), and drugs can all modify effects of ANS control, as can cerebral cortical influences such as stress, anxiety, and fear. Increased venous volume that causes an increase in right atrial volume and wall stretch may elicit an increase in heart rate (if the resting heart rate is low). Regular cardiac arrhythmias are frequently associated with respiration. Inspiration causes an increase in heart rate, while the heart rate slows during expiration. Stimulation of chemoreceptors associated with respiratory control by hypoxia, hypercapnea, or acidosis also cause an increase in both heart rate and respiration.

14. CONTROL OF BLOOD FLOW IN THE PERIPHERAL CIRCULATION Peripheral tissue blood flow is controlled by changes in vascular resistance. Resistance, in turn, can be altered by changes in activity of the sympathetic portion of the ANS and/or by changes in the local environment through which blood vessels pass.

15. CONTROL OF BLOOD FLOW IN THE PERIPHERAL CIRCULATION The blood contained within the arterial system approximates 15% to 20% of the total blood volume and must be allocated to various regions of the body sparingly. Selective distribution is accomplished by the arterioles, which control regional blood flow. Control of flow is accomplished by: a) ANS and hormones, which are generally under central control. b) Factors that are released and act at the local level.

16. LOCAL CONTROL OF BLOOD FLOW Local control involves changes in the tension developed in vascular smooth muscle in blood vessel walls. Some tissues exhibit a high degree of tone (skin, resting skeletal muscle), while others have little tone in the resting state (cerebral and coronary vessels). Many (but not all) tissues use this property of tone to change flow to meet their metabolic needs. Such tissues are said to exhibit autoregulation of blood flow. They resist permanent changes in flow caused by increases or decreases in pressure. If flow is adequate to meet the metabolic needs of the tissue at that time, changes in pressure produce only transient changes in flow.

18. LOCAL CONTROL OF BLOOD FLOW The tissue has autoregulated its flow because the increased pressure caused overperfusion (the vessels responded by constricting), while decreased pressure caused underperfusion (the response is dilation). The mechanisms responsible for this phenomenon: a) increased tissue pressure - tissue edema causes extravascular compression b) myogenic effect - stretch of the vascular smooth muscle causes contraction of that muscle c) vasodilator metabolite release - substances released at the local level cause relaxation of smooth muscle at the local level

19. CIRCULATING HORMONES OR HUMORAL AGENTS Vasodilators such as bradykinin and histamine may be produced and released at one site, get into the circulation, and have an effect at another site (dilation). Under certain conditions, epinephrine, a beta 2 receptor agonist, can also cause vasodilation. Vasoconstrictors also have an effect on vascular smooth muscle. Norepinephrine from the adrenal medulla, angiotensin II produced by the action of renin from the kidney, and vasopressin (antidiuretic hormone, ADH) released from the pituitary all cause constriction if adequate amounts are present.

20. NEURAL CONTROL OF PERIPHERAL BLOOD FLOW Efferent fibers are involved in changing vascular resistance and they fall into two categories: sympathetic vasoconstrictor fibers sympathetic vasodilator fibers

21. SYMPATHETIC VASOCONSTRICTOR FIBERS Preganglionic fibers exit the cord from T 1 to L 3 , and postganglionic fibers originate in the sympathetic ganglia. They have a low resting discharge rate (1 to 2 per sec) and thus impart some degree of nervous 'tone' to vascular smooth muscle. Maximal contraction occurs at about 10 impulses/sec and the neurotransmitter is norepinephrine (NE). Some adrenergic fibers release additional transmitters that include ATP, and neuropeptide Y (NPY). These fibers supply arteries, arterioles, and veins, but not capillaries. Stimulation of these efferent fibers can cause significant venoconstriction and increased arteriolar resistance. The general effect on large arteries is small (arteries do not constrict enough to change resistance), but they do cause a decrease in arterial compliance. The primary function of these fibers is to regulate the resistance in vessels involved in blood pressure and temperature regulation. Decrease in resistance (vasodilation) is induced by a decrease in activity in these fibers.

22. SYMPATHETIC VASODILATOR FIBERS These fibers have a limited distribution (skeletal muscle vascular beds) and, where present, they run with constrictor fibers and release ACh (i.e., are cholinergic). They originate in the motor cortex (not in the vasomotor center) and they are apparently activated in anticipation of exercise and in response to threatening situations (arousal reaction). Activation opens vascular shunts, which permits an increase in muscle blood flow prior to the onset of exercise.

23. SYMPATHETIC VASODILATOR FIBERS Other fibers also release ACh and cause dilation, but these are parasympathetic and are distributed to genitalia and some glands. No parasympathetic fibers are involved in the normal regulation of blood pressure via resistance changes.

25. COMPONENTS OF NERVOUS CONTROL OF ARTERIAL BLOOD PRESSURE Long-term regulation of blood pressure involves body fluid balance, which is a function of the kidneys. Short-term regulation is a function of the cardiovascular system. Effective regulation of ABP involves the ability to monitor the pressure (sensors), a system to assess the correctness of the pressure (integrating center), and mechanisms to adjust the pressure to the required level (effectors). These components, along with their communicating fibers, comprise a reflex arc that is used in day-to-day blood pressure regulation.

26. COMPONENTS: EFFECTORS Effectors include vascular smooth muscle in arteries, arterioles, and veins. The latter two vessels are by far the most important in blood pressure regulation. The other effector is the heart, which receives both sympathetic and parasympathetic input (the effects of ANS on the rate, the contractility, and the rate of pressure development).

27. COMPONENTS: SENSORS Sensors include stretch receptors (or baroreceptors or pressoreceptors). These receptors are located in the wall of the carotid sinus and the aortic arch. The receptors are modified nerve endings, and distortion (stretch) increases the frequency of action potentials in their fibers, while decreased stretch does the opposite. Afferent signals from the carotid sinus are carried in the carotid sinus nerve (nerve of Hering - a branch of cranial nerve IX), or from the aortic arch in the left aortic nerve, which travels in the Vagus. Action potential frequency is fairly linear over a pressure range of from 100 to 180 mmHg. The frequency increases during systole and falls during diastole. The stretch receptors monitor both the absolute pressure and the rate of change of pressure. The receptors are of the slowly adapting type.

28. COMPONENTS: PULMONARY STRETCH RECEPTORS Increased pulmonary artery pressure results in increased efferent activity to the effectors associated with blood pressure regulation. Afferent input from these receptors is to the medulla.

29. COMPONENTS: CARDIAC STRETCH RECEPTORS These receptors are located in the right and left atria. They sense intravascular volume (atrial stretch or preload).Afferent fibers go to the cortex and the hypothalamus. Stretch causes decreased blood pressure and decreased antidiuretic hormone release. Stretch also releases atrial natriuretic peptide, which decreases renin and aldosterone release. Activation of ventricular, pericardial, and coronary sinus stretch receptors causes a reflex fall in pressure .

30. THE REFLEX RESPONSE TO CHANGES IN BLOOD PRESSURE Interventions that lower or raise blood pressure invoke a reflex response that is intended to stabilize blood pressure and heart rate. The system is able to correct perturbations in the system, through negative feedback. For example, if a subject is changed from the supine to the upright posture, cardiac output falls, due to venous pooling (gravity). Arterial blood pressure falls, reducing stretch in the aorta and carotid sinus. The vasomotor center also participates in other complex responses. For instance, immersing the face in cold water elicits bradycardia (the diving reflex). The baroreceptor "set point" is also variable. During sleep, arterial blood pressure pressure falls (10 to 20 mmHg in some cases), yet the vasomotor center makes no attempt to correct for it.

31. CHEMORECEPTORS AND BLOOD PRESSURE The primary function of these receptors is the regulation of respiration. However, they influence blood pressure in some cases. The receptors are in the carotid and aortic bodies and they sense the partial pressures of O 2 and CO 2 . Moderate changes in blood levels of these gases affect respiration, but extreme changes may alter blood pressure. Hypoxia and hypercapnea cause blood pressure to increase.

32. CHEMORECEPTORS AND BLOOD PRESSURE Chemoreceptors also are sensitive to flow, so that even if blood gas levels are normal, hypotension (which results in low blood flow) may result in increased pulmonary ventilation.

33. CHEMORECEPTORS AND BLOOD PRESSURE Cerebral chemoreceptors also sense O 2 and CO 2 levels in brain tissue. They are especially sensitive to CO 2 levels and, when stimulated, cause an increase in blood pressure (because of tachycardia). They may provide a backup emergency system in extreme hypotension.

34. OTHERS PRESSOR RESPONSES Strong stimulation of a peripheral sensory nerve fiber can elicit a pressor response. This is probably due to stimulation of pain fibers. Stimulation of 'deep pain' fibers from viscera and large blood vessels may elicit a very strong depressor response and actually cause fainting (Vasovagal Syncope)

37. INTEGRATION OF BLOOD PRESSURE RESPONSES A loose organization of neurons in the medulla comprise the Vasomotor Center (VMC). It is composed of pressor (P) and depressor (D) areas, which communicate with one another and with sympathetic neurons in the spinal cord. This center receives inputs from sensors and, in addition, input from the cortex and hypothalamus. Stimulation of the pressor area causes an increase in rate, force of contraction of the heart, and constriction of vascular smooth muscle in arterioles and veins (increased venomotor tone). Stimulation of the depressor area has the opposite effect.

38. INTEGRATION OF BLOOD PRESSURE RESPONSES These effects are mediated via sympathetic fibers. Parasympathetic fibers do not emanate from the vasomotor center (VMC), but arise directly from the Vagal centers. Fibers also reach the VMC from the hypothalamus. These fibers are involved in temperature regulation (efferents to skin blood vessels) and those from the cortex to the VMC influence vascular changes in response to anger (rate and pressure changes), embarrassment (blushing), and so forth.

39. INTEGRATION OF BLOOD PRESSURE RESPONSES Vasomotor Center ( in medulla) - oversees changes in blood vessel diameter Vasomotor activity modified by imputs from : baroreceptors = pressure sensitive mechanoreceptors which respond to changes in arterial pressure and stretch chemoreceptors = detect changes in levels of CO 2 , O 2 , H + higher brain centers (hypothalamus, cerebrum) - get involved in stress or exercise situations

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