Cardiovascular Physiology Qiang XIA (夏强), MD & PhD Department of Physiology Room C518, Block C, Research Building, School of Medicine Tel: 88208252 Email: xiaqiang@zju.edu.cn

Regulation of Cardiovascular Activities Lecture Outline Nervous Regulation Humoral Regulation Autoregulation

Nervous Regulation

Innervation of cardiovascular system

Nervous regulation of the circulation

Cardiac mechanisms of norepinephrine

Mechanisms of norepinephrine —increase Na+ & Ca2+ permeability If , phase 4 spontaneous depolarization, autorhythmicity  Ca2+ influx , phase 0 amplitude & velocity , conductivity  Ca2+ influx , Ca2+ release , [Ca2+ ]i , contractility 

Asymmetrical innervation of sympathetic nerve

Cardiac mechanisms of acetylcholine

Mechanisms of acetylcholine —increase K+ & decrease Ca2+ permeability K+ outward , |MRP| , phase 4 spontaneous depolarization , autorhythmicity  Inhibition of Ca2+ channel, phase 0 amplitude & velocity , conductivity  Ca2+ influx , [Ca2+ ]i , contractility 

Cardiac effect of parasympathetic stimulation

Interaction of sympathetic and parasympathetic nerves

Predominance of autonomic nerves

Cardiovascular Center A collection of functionally similar neurons that help to regulate HR, SV, and blood vessel tone

Vasomotor center Located bilaterally mainly in the reticular substance of the medulla and of the lower third of the pons Vasoconstrictor area Vasodilator area Cardioinhibitor area – dorsal nuclei of the vagus nerves and ambiguous nucleus Sensory area – tractus solitarius

Vasomotor center

Higher cardiovascular centers Reticular substance of the pons Mesencephalon Diencephalon Hypothalamus Cerebral cortex Cerebellum

Baroreceptor Reflexes Arterial baroreceptors Carotid sinus receptor Aortic arch receptor Afferent nerves (Buffer nerves) Cardiovascular center: medulla Efferent nerves: cardiac sympathetic nerve, sympathetic constrictor nerve, vagus nerve Effector: heart & blood vessels

Baroreceptor neurons function as sensors in the homeostatic maintenance of MAP by constantly monitoring pressure in the aortic arch and carotid sinuses.

Characteristics of baroreceptors: Sensitive to stretching of the vessel walls Proportional firing rate to increased stretching Responding to pressures ranging from 60-180 mmHg Receptors within the aortic arch are less sensitive than the carotid sinus receptors

The action potential frequency in baroreceptor neurons is represented here as being directly proportional to MAP.

i.e., reduce cardiac output i.e., MAP is above homeostatic set point i.e., reduce cardiac output Baroreceptor neurons deliver MAP information to the medulla oblongata’s cardiovascular control center (CVCC); the CVCC determines autonomic output to the heart.

Reflex pathway

Typical carotid sinus reflex

Physiological Significance Maintaining relatively constant arterial pressure, reducing the variation in arterial pressure

Humoral Regulation Vasoconstrictor agents Vasodilator agents

Renin-angiotensin system

Juxtaglomerular cell Renin

Physiological effects of angiotensin II Constricts resistance vessels Acts upon the adrenal cortex to release aldosterone Stimulates the release of vasopressin Facilitates norepinephrine release from sympathetic nerve endings Stimulates thirst centers within the brain

Epinephrine & Norepinephrine Sources Epinephrine---- adrenal medulla Norepinephrine---- sympathetic nerves

Catecholamines Norepinephrine Epinephrine

Effects Epinephrine Norepinephrine Receptor a-adrenoceptor ++ +++ b-adrenoceptor ++ + Heart heart rate + + (in vitro) － (in vivo) cardiac output +++ ± Vessels constriction (skin, visceral) + +++ relaxation (SM, liver) － +++ total peripheral resistance ± +++ Blood pressure systolic +++ +++ diastolic ± ++ MAP + ++ Clinical application positive inotropic pressor agent agent

A 23-year-old woman presents to your emergency service with an anaphylactic reaction after being stung by several bees. She complains of wheezing and shortness of breath. On examination, the client is in acute distress. BP is 98/56 mmHg, PR 110/min, RR 28/min, and temperature 98.7°F. She is immediately treated with supplemental oxygen. In treating this condition further, what drug is required most urgently? A Theophylline B Glucagon C Cimetidine D Methylprednisolone E Epinephrine

Vasopressin (antidiuretic hormone, ADH)

Endothelium-derived vasoactive substances Vasodilator factors PGI2--prostacyclin EDRF, NO--endothelium-derived relaxing factor, nitric oxide EDHF--endothelium-dependent hyperpolarizing factor Vasoconstrictor factors Endothelin

Atrial natriuretic peptide (ANP) Produces natriuresis and diuresis Decreases renin release Reduces total peripheral resistance via vasodilatation Decreases heart rate, cardiac output

Autoregulation Definition: Intrinsic ability of an organ to maintain a constant blood flow despite changes in perfusion pressure, independent of any neural or humoral influences

The End.