Objectives have been taken from The American Physiological Society Medical Curri culum Objectives Project http//:www.the-aps.org/education/MedPhysObj/medcor.

htm In some case, the order of the topics and the objectives have been modify Objectives: 1. List the anatomical components of the baroreceptor reflex. 2. Exp lain the sequence of events in the baroreceptor that occur after an acute increa se or decrease in arterial blood pressure. Include receptor response, afferent n erve activity, CNS integration, efferent nerve activity to SA node, ventricles, arterioles, venules , and hypothalamus. 3. Contrast the sympathetic and parasymp athetic nervous system control of the heart rate, contractility, TPR, and venous capacitance. Predict the cardiovascular consequence of altering sympathetic ner ve activity and parasympathetic nerve activity 4. Outline the cardiovascular ref lexes initiated by decreases in blood O2 and increases in blood CO2. 5. CNS isch emic response. Explain the importance and sequence of events of the CNS ischemic response and the Cushing reaction. 6. Cardiopulmonary receptors. Explain the se quence of events mediated by cardiopulmonary (volume) receptors that occur after an acute increase or decrease in arterial blood pressure. Include receptor resp onse, afferent nerve activity, CNS integration efferent nerve activity to the he art, kidney, hypothalamus, and vasculature. 7. Describe the release, cardiovascu lar target organs, and mechanisms of cardiovascular effects for Angiotensin, ANF , EDRF. 8. Kidney in long term regulation of BP. Explain the role of the kidney in the long term regulation of arterial pressure. 9. Contrast the relative contr ibution of short-and long term mechanisms in blood pressure and blood volume reg ulation CV 121

CENTRAL REGULATORY RESPONSE OF THE HEART AND THE VASCULATURE Introduction The ca rdiovascular system is organized to respond to multiple demands simultaneously, and specially to meet crises. Intrinsic mechanism within tissue stabilize tissue flow and capillary pressure within organs. At the same time, extrinsic mechanis m operating via nerves and hormones coordinate functional needs of the organism as a whole. For example, fear causes neurally mediated constriction of most vasc ular beds. Generalized vasoconstriction mobilizes blood from fight-or-flight, wh ile is the heart and striated muscle, intrinsic mechanism can override the vasoc onstrictor signals to allow the muscles to do the work of escaping. In time of c risis the vascular function of all organs will be sacrificed to maintain the cer ebral blood flow and to permit the animal or person to escape. I. A. B. C. ATORY CENTERS Vasomotor or vasoconstrictor center - the pressor areaIs the major integrative area for all central nervous system control Regulates cardiac funct ion with both the sympathetic and parasympathetic nervous outflow. Located in th e dorsal medulla Stimulation causes: cardioacceleration, vasoconstriction, incre ased myocardial contractility Generates continuous low level of neural ctivity i n the sympathetic fibers which causes vasoconstriction (sympathetic tone) Tonic activity is modulated by a wide variety of inputs from chemoreceptor and barorec eptors throughout the body Vasomotor center the depressor area-Located in the ven tromedial and caudal region of the medulla Caused dilation mediated by the actio n through vasomotor center and through spinal pathways Hypothalamus Integrative center for various regulatory processes such a s temperature control Stimulation of the anterior hypothalamus causes decreased blood pressure, vasodilation, and bradycardia Stimulation of the posterolateral hypothalamus causes tachycardia a nd vasocostriction Cutaneous thermal receptors induce vasodilation or vasoconstr iction in response to heat and cold respectively CV 122

II. Blood pressure control system Overall aim of the system is to keep aortic pressure constant and let the organs regulate their own flow through autoregulation. A. Blood pressure control is ba sed on negative feedback that requires: A detector (sensor receptor) Afferent ne ural pathway An integrator or coordinating center An efferent neural pathway and An effector B. Integrator or coordinating center Pressure information from the peripheral baror eceptors is integrated in the medulla of the brainstem. The first synapse for al l afferent signals is in the Nucleus tractus solitarius (NTS) CV 123

 Activity in the NTS activates neurons in the dorsal motor nucleus of the vagus ( DMV). That in turn Activates parasympathetic vagal efferent fibers to the heart. Activity in the NTS also activates neurons in the nucleus ambiguous. That also activates vagal efferent fibers to the heart. Activity in the NTS also inhibits neurons in the C1 region of the vasomotor area. The outflow from this area is sy mpathetic innervation to the peripheral blood vessels, the heart and the adrenal medulla. The short term control mechanism of blood pressure (neural) are: Baror eceptor reflexes Chemoreceptor reflexes CNS ischemic response (reflex) Cushing r eaction Atrial and pulmonary artery reflexes (low pressure receptors) Atrial ref lex to kidney Bain-bridge reflex III. 1. 2. 3. 4. 5. 1. Baroreceptor reflexes Peripheral baroreceptors (stretch receptors) detect a change in the blood pressu re. They send their signals to the medulla which compares the actual pressure to an internal set point. The medulla then sends information over the autonomic ne rves to stimulate or inhibit the blood vessels and heart as is required. That in turn returns the blood pressure to the set point. CV 124

A. Sensor: Arterial baroreceptors Location: carotid sinus and arch of aorta Stim ulus: stretch of the vessel B. Afferent pathway 1. Stretch receptors in the wall s of the carotid sinuses. These receptors are innervated by the Herrings nerve (b ranch of the glossopharyngeal. a. Increased blood pressure stretches the walls a nd increases their frequency of action potentials. A fall in pressure decreases the frequency. b. Are rate-sensitive and respond to pulsatile pressures better t han a steady pressure particularly at low mean pressures 2. The aortic arch has similar receptors that are innervated by the aortic nerve, a branch of the vagus . 3. The Aortic baroreceptors stop firing at pressures below 100 mmHg while caro tid sinus receptors continue firing all the way down to 50 mmHg. Both saturate a t about 200 mmHg Then carotid baroreceptors are more sensitive than aortic CV 125

4. The baroreceptors are sensitive to both mean (MAP) and pulse pressure (PP) Th e figure to the right shows the nerve discharge along the glossopharyngeal nerve to the medulla. The baroreflex acts primarily to control minute-to-minute blood Pressure (pressure changes). The baroreceptors quickly adapt to long-term chang es in pressure. C. Effectors 1. Heart 2. Blood vessels D. Efferent Pathway 1. Sympathetic nervou s system acts to increase pressure by increasing heart rate, contractility and c onstricting the arteries and veins 2. Parasympathetic nervous system acts to dec rease pressure by slowing heart rate. Acetylcholine acts to inhibit cAMP in the heart and lowers contractility. The human ventricle receive very few vagal fiber s as a result the parasympathetic causes only a very light decrease in contracti lity. In order to decrease contractility the CNS can do it only by a decrease sy mpathetic tone. PS do not have effect on the vasculature. A reduction in MAP or PP causes constriction of both arterioles and venules. Measurements are made whi le manipulating the MAP and PP. The nerve fires with each rise in the arterial p ressure. Also the number of spikes with each pulse increases as the MAP increase s. E. Function of baroreceptors in body posture changes. When a person stand up after having been lying down, the arterial pressure in the upper parts of the bo dy tends to drop and sometimes the patient has loss of consciousness. This becau se of gravity effect that pulls down blood This drop in pressure immediately cau ses a decrease in baroreceptors activity and an CV 126

then a strong sympathetic activity to vessels and heart to return to normal the blood pressure in the upper part of the body. F. Clamping of both carotid arteri es In a dog, the clamping of both common carotid arteries (after cutting the two vagus nerves), causes a drop in sinus pressure, then baroreceptors are inactiva ted and the VMC increase its activity causing the sympathetic stimulation to the heart and vessels and blood pressure will remain elevated during the time the c arotid occlusion is maintained. When the occlusion is release the aortic pressur e falls below the normal as overcompensation and then return to normal. G. Blood pressure increases with exercise. With exercise the working muscles increases t he blood flow by active hyperemia, the peripheral resistances drop and thus the blood pressure. Baroreceptors detect the drop in BP and initiate a reflex to ret urn pressure back toward the set point pressure but not pass it. In heavy exerci se, however, pressure will actually be higher than before the start of the exerc ise. That is because the CNS actually increases the set point during heavy exerc ise. 2. Peripheral chemoreceptors (carotid and aortic bodies). This is an important m echanism for maintaining arterial blood pO2, pCO2, and pH within appropriate phy siological ranges. Carotid and aortic bodies are stimulated by: 1. Low PO2 (hypo xemia) 2. High PCO2 (hypercapnia) 3. Low pH A. Stimulation of the chemoreceptors directly decreases heart rate and constricts the peripheral blood vessels. CV 127

Generally systemic hypoxia causes a tachycardia due to the increased respiratory activity . The overall effect is to raise the blood pressure. B. Circulatory sh ock and respiratory failure (conditions that decrease arterial pO2 and pH, and i ncrease PaCO2) dramatically increase chemoreceptor activity leading to enhanced sympathetic outflow to the heart and vessels via activation of the vasomotor cen ter. C. The threshold pO2 for activation is about 80 mmHg (normal arterial pO2 i s about 95 mmHg). Any elevation of pCO2 above a normal value of 40 mmHg, or a de crease in pH below 7.4 causes receptor firing. If respiratory activity is not al lowed to change during chemoreceptor stimulation (thus removing the influence of lung mechanoreceptors), then chemoreceptor activation causes bradycardia and co ronary vasodilation (both via vagal activation) and systemic vasoconstriction (v ia sympathetic activation). If respiratory activity increases, then sympathetic activity stimulates both the heart and vasculature to increase arterial pressure . 3. Ischemic response of the CNS. A. Is an emergency control system. Cerebral i schemia at the level of the VMC causes the neurons of the VMC strongly become ac tivated, this produces a drastic increase in MAP to maximal possible level (some times 250 mmHg). The extreme excitation of the VMC neurons is caused probably by increased local concentration of CO2 as consequence of the low blood flow what elicit a strong and powerful sympathetic stimulation to the vasomotor nervous co ntrol areas in the brain. B. The ischemic response of the CNS becomes activated when the MAP falls down 60 mmHg. Reaching the greatest stimulation with MAP of 1 5 to 20 mmHg. 4. Cushing reaction A. Special type of CNS ischemic response is ac tivated by an increase in intra cranial pressure that can occur from increase in CSF pressure, edema of the brain or an intercranial bleed. The increased pressu re collapses the blood vessels within the vault . The ischemia in the CNS causes intense stimulation of both the sympathetic and parasympathetic outflow. Becaus e the sympathetic system has the more profound effect on blood pressure, blood p ressure becomes quite high in an attempt to restore the blood flow into the brai n. Because theacetylcholine can inhibit norepinephrines effect at the SA node the heart rate will tends to decrease. Thus the patient will present with a bradyca rdia and a hypertension. 5. Cardiopulmonary mechanoreceptors Low pressure recept ors (A and B type) are located in the left atrium. A fibers are stimulated by at rial systole while B fibers are stimulated by atrial distention (increase in vol ume). Atrial stretch activates B fibers which: 1. Increases the heart rate (Bain bridge reflex) through a neural reflex. Atrial stretch also increases the rate b y a direct mechanical effect on the SA node. The Bainbridge reflex is about 50% direct and 50% neural effect. The overall effect is to detect buildup of blood b ehind the heart and move it forward. 2. Decreases sympathetic tone to the kidney causing increased filtration and urine formation. 3. Decreased production of va sopressin (anti-diuretic hormone) to promote fluid loss at the kidney. 4. Atrial stretch directly causes production of atrial naturetic peptide (ANP) by the atr ial cells. This causes dilation of blood vessels and loss of sodium and water by the kidney. The overall effect (2-4 above) is to cause reduced blood volume whe n the atria are distended and to decrease MAP. CV 128

IV. Long term regulation of arterial blood pressure. The kidneyA. The kidney is the p rimary controller of long term arterial blood pressure. Arterial pressure direct ly determines fluid loss at the kidney and thus the kidney controls blood pressu re by a negative feedback system. Salt (and therefore fluid volume) loss at the kidney is highly dependent on blood pressure and relatively independent of salt intake. B. Renin-Angiotensin system While some of the kidneys control is direct t hrough the effect of arterial pressure on glomerular filtration, the majority is indirect through the Rennin-Angiotensin system. Low blood flow to the kidney ca uses secretion of Renin. Renin causes the conversion of Angiotensinogen in the b lood to Angiotensin I. This is quickly cleaved by ACE in the lungs to the powerf ul vasoconstrictor Angiotensin II (AII). Besides the action of AII as powerful c onstrictor of the peripheral vessels it also causes the kidney to retain fluid a nd thus Guyton Hall. Medical Physiology 11 Ed. th increase blood volume. People with essential hypertension have an elevated set p oint for fluid loss. Those that are salt-sensitive also have a decreased slope i n the renal function curve. The baroreceptor reflex will quickly adapt (within 3 days) if the kidneys set point is raised CV 129

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