Introduction to the Cardiovascular System - part 6 docx

epinephrine are different because epinephrine binds to ␣-adrenoceptors as well as to ␤- adrenoceptors. Increasing concentrations of epinephrine result in further cardiac stimulation along with ␣-adrenoceptor mediated activation of vascular smooth muscle leading to vasoconstriction. This increases arterial blood pressure (pressor response) owing to both an increase in cardiac output and an increase in systemic vascular resistance. Circulating norepinephrine affects the heart and systemic vasculature by binding to ␤ 1 , ␤ 2 , ␣ 1 , and ␣ 2 adrenoceptors; however, the affinity of norepinephrine for ␤ 2 and ␣ 2 - adrenoceptors is relatively weak. Therefore, the predominant affects of norepinephrine are mediated through ␤ 1 and ␣ 1 -adrenoceptors. If norepinephrine is injected intra- venously, it causes an increase in mean arterial blood pressure (systemic vasoconstriction) and pulse pressure (owing to increased stroke volume) and a paradoxical decrease in heart rate after an initial transient increase in heart rate (Fig. 6-9; Table 6-3). The transient increase in heart rate is due to norepinephrine binding to ␤ 1 -adrenoceptors in the sinoatrial node, whereas the secondary bradycardia is due to a baroreceptor reflex (vagal-mediated), which is in response to the increase in arterial pressure. High levels of circulating catecholamines, caused by a catecholamine-secreting adrenal tumor (pheochromocytoma), causes tachycardia, arrhythmias, and severe hypertension (systolic arterial pressures can exceed 200 mm Hg). Other actions of circulating catecholamines include (1) stimulation of renin release with subsequent elevation of angiotensin II (AII) and aldosterone, and (2) cardiac and vascular smooth muscle hypertrophy and remodeling. These actions of catecholamines, in addition to the hemodynamic and cardiac actions already described, make them a frequent therapeutic target for the treatment of hypertension, heart failure, coronary artery disease, and arrhythmias. This has led to the development and use of many different types of ␣ and ␤-adrenocep- NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION 131 How would the changes in arterial pressure and heart rate shown in Figure 6-8 be different if ␤ 1 -adrenoceptors were blocked before the administration of low-dose epinephrine? ␤ 1 -adrenoceptor activation is responsible for the tachycardia and increased cardiac output produced by epinephrine. Blocking ␤ 1 -adrenoceptors would abolish this response. Epinephrine also binds to vascular ␤ 2 -adrenoceptors to cause vasodilation; therefore arterial pressure would fall during epinephrine infusion in the presence of ␤ 1 -adrenoceptor blockade because the decrease in systemic vascular resistance would not be offset by an increase in cardiac output. PROBLEM 6-2 How would the norepinephrine-induced changes in arterial pressure and heart rate shown in Figure 6-9 be different in the presence of bilateral cervical vagotomy? Bilateral cervical vagotomy would prevent vagal slowing of the heart and denervate the aortic arch baroreceptors. Heart rate (and inotropy) would increase owing to norepinephrine binding to ␤ 1 -adrenoceptors on the heart that is now unopposed by the vagus. This, along with aortic arch denervation, would enhance the pressor response of norepinephrine. PROBLEM 6-3 Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 131 tor antagonists to modulate the effects of circulating catecholamines as well as the norepinephrine released by sympathetic nerves. Renin-Angiotensin-Aldosterone System The renin-angiotensin-aldosterone system plays an important role in regulating blood volume, cardiac and vascular function, and arterial blood pressure. Although the pathways for renin and angiotensin formation have been found in a number of tissues, the most important site for renin formation and subsequent formation of circulating angiotensin is the kidney. Sympathetic stimulation of the kidneys (via ␤ 1 -adrenoceptors), renal artery hypotension, and decreased sodium delivery to the distal tubules (usually caused by reduced glomerular filtration rate secondary to reduced renal perfusion) stimulate the release of renin into the circulation. The renin is formed within, and released from, juxtaglomerular cells associated with afferent and efferent arterioles of renal glomeruli, which are adjacent to the mac- ula densa cells of distal tubule segments that sense sodium chloride concentrations in the distal tubule. Together, these components are referred to as the juxtaglomerular apparatus. Renin is an enzyme that acts upon angiotensinogen, a circulating substrate synthesized and released by the liver, which un- dergoes proteolytic cleavage to form the de- capeptide angiotensin I. Vascular endothe- lium, particularly in the lungs, has an enzyme, angiotensin-converting enzyme (ACE), that cleaves off two amino acids to form the octapeptide, angiotensin II. Angiotensin II has several important functions that are mediated by specific angiotensin II receptors (AT 1 ) (Figure 6-10). It 1. Constricts resistance vessels, thereby increasing systemic vascular resistance and arterial pressure. 2. Facilitates norepinephrine release from sympathetic nerve endings and inhibits norepinephrine re-uptake by nerve endings, thereby enhancing sympathetic adrenergic affects. 3. Acts upon the adrenal cortex to release aldosterone, which in turn acts upon the kidneys to increase sodium and fluid retention, thereby increasing blood volume. 4. Stimulates the release of vasopressin from the posterior pituitary, which acts upon the kidneys to increase fluid retention and blood volume. 5. Stimulates thirst centers within the brain, which can lead to an increase in blood volume. 6. Stimulates cardiac and vascular hypertrophy. 132 CHAPTER 6 60 80 100 140 180 100 120 60 FIGURE 6-9 Effects of intravenous administration of a moderate dose of norepinephrine on arterial pressure and heart rate. Norepinephrine increases mean arterial pressure and arterial pulse pressure; heart rate transiently increases (␤ 1 -adrenoceptor stimulation), then decreases owing to baroreceptor reflex activation of vagal efferents to the heart. Mean arterial pressure rises because norepinephrine binds to vascular ␣ 1 -adrenoceptors, which increases systemic vascular resistance. Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 132 Angiotensin II is continuously produced under basal conditions, and this production can change under different physiologic conditions. For example, when a person exercises, circulating levels of angiotensin II increase. An increase in renin release during exercise probably results from sympathetic stimulation of the kidneys. Changes in body posture like- wise alter circulating AII levels, which are increased when a person stands. As with exercise, this results from sympathetic activation. Dehydration and loss of blood volume (hypovolemia) stimulate renin release and angiotensin II formation in response to renal artery hypotension, decreased glomerular filtration rate, and sympathetic activation. Several cardiovascular disease states are associated with changes in circulating angiotensin II. For example, secondary hypertension caused by renal artery stenosis is associated with increased renin release and circulating angiotensin II. Primary hyperal- dosteronism, caused by an adrenal tumor that secretes large amounts of aldosterone, increases arterial pressure through its effects on renal sodium retention. This increases blood volume, cardiac output, and arterial pressure. In this condition, renin release and circulating angiotensin II levels are usually depressed because of the hypertension. In heart failure, circulating angiotensin II increases in response to sympathetic activation and decreased renal perfusion. Therapeutic manipu- lation of the renin-angiotensin-aldosterone system has become important in treating hypertension and heart failure. ACE inhibitors and AT 1 receptor blockers effectively decrease arterial pressure, ventricular afterload, blood volume, and hence ventricular preload, and they inhibit and reverse cardiac and vascular remodeling that occurs during chronic hypertension and heart failure. Note that local, tissue-produced angiotensin may play a significant role in cardiovascular pathophysiology. Many tissues and organs, including the heart and blood vessels, can produce renin and angiotensin II, which have actions directly within the tissue. This may explain why ACE inhibitors can reduce arterial pressure and cause cardiac and vascular remodeling (e.g., diminish hypertrophy) even in individuals who do not have elevated NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION 133 Renin A II Arterial Pressure Aldosterone ↑ Renal Sodium & Fluid Retention Angiotensinogen Sympathetic Stimulation Hypotension Sodium Delivery ACE Systemic Vasoconstriction Blood Volume A I Kidney Cardiac Output Cardiac & Vascular Hypertrophy Adrenal Cortex ↓ ↑ ↑ Thirst FIGURE 6-10 Formation of angiotensin II and its effects on renal, vascular, and cardiac function. Renin is released by the kidneys in response to sympathetic stimulation, hypotension, and decreased sodium delivery to distal tubules. Renin acts upon angiotensinogen to form angiotensin I (AI), which is converted to angiotensin II (AII) by angiotensin- converting enzyme (ACE). AII has several important actions: it stimulates aldosterone release, which increases renal sodium reabsorption; directly stimulates renal sodium reabsorption; stimulates thirst; produces systemic vasoconstriction; and causes cardiac and vascular smooth muscle hypertrophy. The overall systemic effect of increased AII is increased blood volume, venous pressure, and arterial pressure. Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 133 circulating levels of angiotensin II. In hypertension and heart failure, for example, tissue ACE activity is often elevated, and this may be the primary target for the pharmacologic actions of ACE inhibitors. Atrial Natriuretic Peptide Atrial natriuretic peptide (ANP) is a 28-amino acid peptide that is synthesized, stored, and released by atrial myocytes in response to atrial distension, angiotensin II stimulation, endothelin, and sympathetic stimulation (␤- adrenoceptor mediated). Therefore, elevated levels of ANP are found during conditions such as hypervolemia and congestive heart failure, both of which cause atrial distension. ANP is involved in the long-term regulation of sodium and water balance, blood volume, and arterial pressure (Figure 6-11). Most of its actions are the opposite of angiotensin II, and therefore ANP is a counter-regulatory system for the renin- angiotensin-aldosterone system. ANP decreases aldosterone release by the adrenal cortex; increases glomerular filtration rate; produces natriuresis and diuresis (potassium sparing); and decreases renin release, thereby decreasing angiotensin II. These actions reduce blood volume, which leads to a fall in central venous pressure, cardiac output, and arterial blood pressure. Chronic elevations of ANP appear to decrease arterial blood pressure primarily by decreasing systemic vascular resistance. The mechanism of systemic vasodilation may involve ANP receptor-mediated elevations in vascular smooth muscle cGMP (ANP activates particulate guanylyl cyclase). ANP also attenuates sympathetic vascular tone. This latter mechanism may involve ANP acting upon sites within the central nervous system as well as through inhibition of norepinephrine release by sympathetic nerve terminals. A new class of drugs that are neutral endopeptidase (NEP) inhibitors may be useful in treating heart failure. By inhibiting NEP, the enzyme responsible for the degradation of ANP, these drugs elevate plasma levels of ANP. NEP inhibition is effective in some models of heart failure when combined with 134 CHAPTER 6 ↓ Aldosterone ↓ Angiotensin II ↓ Renin Release Natriuresis Diuresis ↑ GFR ↓ ↓ CO ↓ ↓ SVR Degradation Atrial distension Sympathetic stimulation Angiotensin II Endothelin NEP Blood Volume CVP ↓ ANP Arterial Pressure FIGURE 6-11 Formation and cardiovascular/renal actions of atrial natriuretic peptide (ANP). ANP, which is released from cardiac atrial tissue in response to atrial distension, sympathetic stimulation, increased angiotensin II, and endothelin, functions as a counter-regulatory mechanism for the renin-angiotensin-aldosterone system. ANP decreases renin release, angiotensin II and aldosterone formation, blood volume, central venous pressure, and arterial pressure. NEP, neutral endopeptidase; GFR, glomerular filtration rate; CVP, central venous pressure; CO, cardiac output; SVR, systemic vascular resistance. Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 134 an ACE inhibitor. The reason for this is that NEP inhibition, by elevating ANP, reinforces the effects of ACE inhibition. Brain-type natriuretic peptide (BNP), a 32- amino acid peptide hormone related to ANP, is synthesized and released by the ventricles in response to pressure and volume overload, particularly during heart failure. BNP appears to have actions that are similar to those of ANP. Recently, circulating BNP has been shown to be a sensitive biomarker for heart failure. Vasopressin (Antidiuretic Hormone) Vasopressin (arginine vasopressin, AVP; antidiuretic hormone, ADH) is a nonapeptide hormone released from the posterior pituitary (Figure 6-12). AVP has two principal sites of action: the kidneys and blood vessels. The most important physiologic action of AVP is that it increases water reabsorption by the kidneys by increasing water permeability in the collecting duct, thereby permitting the formation of concentrated urine. This is the NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION 135 A 56-year old male patient is found to have an arterial pressure of 190/115 mm Hg. Two years earlier he was normotensive. Diagnostic tests reveal bilateral renal artery stenosis. Describe the mechanisms by which this condition elevates arterial pressure. Bilateral renal artery stenosis reduces the pressure within the afferent arterioles, which causes release of renin. This, in turn, increases circulating angiotensin II, which stimulates aldosterone release. Activation of the renin-angiotensin-aldosterone system causes sodium and fluid retention by the kidneys and an increase in blood volume, which increases cardiac output. Increased vasopressin (stimulated by angiotensin II) contributes to the increase in blood volume. Increased angiotensin II increases systemic vascular resistance by binding to vascular AT 1 receptors and by enhancement of sympathetic activity. These changes in cardiac output and systemic vascular resistance lead to a hypertensive state. CASE 6-1 Angiotensin II Hyperosmolarity Decreased atrial receptor firing Sympathetic stimulation Vasoconstriction Pituitary Renal Fluid Reabsorption Increased Blood Volume Increased Arterial Pressure Vasopressin FIGURE 6-12 Cardiovascular and renal effects of arginine vasopressin (AVP). AVP release from the posterior pituitary is stimulated by angiotensin II, hyperosmolarity, decreased atrial receptor firing (usually in response to hypovolemia), and sympathetic activation. The primary action of AVP is on the kidney to increase water reabsorption (antidiuretic effect), which increases blood volume and arterial pressure. AVP also has direct vasoconstrictor actions at high concentrations. Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 135 antidiuretic property of AVP, and it leads to an increase in blood volume and arterial blood pressure. This hormone also constricts arterial blood vessels; however, the normal physiologic concentrations of AVP are below its va- soactive range. Studies have shown, nevertheless, that in severe hypovolemic shock, when AVP release is very high, AVP contributes to the compensatory increase in systemic vascular resistance. Several mechanisms regulate the release of AVP. Specialized stretch receptors within the atrial walls and large veins (cardiopul- monary baroreceptors) entering the atria decrease their firing rate when atrial pressure falls (as occurs with hypovolemia). Afferents from these receptors synapse within the hypothalamus, which is the site of AVP synthe- sis. AVP is transported from the hypothalamus via axons to the posterior pituitary, from where it is secreted into the circulation. Atrial receptor firing normally inhibits the release of AVP. With hypovolemia and decreased central venous pressure, the decreased firing of atrial stretch receptors leads to an increase in AVP release. AVP release is also stimulated by enhanced sympathetic activity accompany- ing decreased arterial baroreceptor activity during hypotension. An important mechanism regulating AVP release involves hypo- thalamic osmoreceptors, which sense extra- cellular osmolarity. When osmolarity rises, as occurs during dehydration, AVP release is stimulated. Finally, angiotensin II receptors located within the hypothalamus regulate AVP release; an increase in angiotensin II stimulates AVP release. Heart failure causes a paradoxical increase in AVP. The increased blood volume and atrial pressure associated with heart failure suggest that AVP secretion should be inhibited, but it is not. It may be that sympathetic and renin- angiotensin system activation in heart failure override the volume and low pressure cardiovascular receptors (as well as the osmoregula- tion of AVP) and cause the increase in AVP secretion. This increase in AVP during heart failure may contribute to the increased systemic vascular resistance and to renal retention of fluid. In summary, the importance of AVP in cardiovascular regulation is primarily through its effects on volume regulation, which in turn affects ventricular preload and cardiac output through the Frank-Starling relationship. Increased AVP, by increasing blood volume, increases cardiac output and arterial pressure. The vasoconstrictor effects of AVP are probably important only when AVP levels are very high, as occurs during severe hypovolemia. INTEGRATION OF NEUROHUMORAL MECHANISMS Autonomic and humoral influences are neces- sary to maintain a normal arterial blood pressure under the different conditions in which the human body functions. Neurohumoral mechanisms enable the body to adjust to changes in body posture, physical activity, or environmental conditions. The neurohumoral mechanisms act through changes in systemic vascular resistance, venous compliance, blood volume, and cardiac function, and through these actions they can effectively regulate arterial blood pressure (Table 6-4). Although each mechanism has independent cardiovascular actions, it is important to understand that each mechanism also has complex interactions with other control mechanisms that serve to reinforce or inhibit the actions of the other control mechanisms. For example, activation of sympathetic nerves either directly or indirectly increases circulating angiotensin II, aldosterone, adrenal catecholamines, and arginine vasopressin, which act together to increase blood volume, cardiac output, and arterial pressure. These humoral changes are accompanied by an increase in ANP, which acts as a counter-regulatory system to limit the effects of the other neurohumoral mechanisms. Finally, it is important to note that some neurohumoral effects are rapid (e.g., autonomic nerves and catecholamine effects on cardiac output and pressure), whereas others may take several hours or days because changes in blood volume must occur before alterations in cardiac output and arterial pressure can be fully expressed. 136 CHAPTER 6 Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 136 SUMMARY OF IMPORTANT CONCEPTS • Autonomic regulation of the heart and vasculature is primarily controlled by special regions within the medulla oblongata of the brainstem that contain the cell bodies of sympathetic and parasympathetic (vagal) efferent nerves. • The hypothalamus plays an integrative role by modulating medullary neuronal activity (e.g., during exercise). • Sensory information from peripheral baroreceptors (e.g., carotid sinus baroreceptors) synapse within the medulla at the nucleus tractus solitarius, which modulates the activity of the sympathetic and vagal neurons within the medulla. • Preganglionic parasympathetic efferent nerves exit the medulla as the tenth cranial nerve and travel to the heart within the left and right vagus nerves. Preganglionic fibers synapse within ganglia located within the heart; short postganglionic fibers innervate the myocardial tissue. Preganglionic sympathetic efferent nerves exit from the spinal cord and synapse within paraverte- bral or prevertebral ganglia before sending out postganglionic fibers to target tissues in the heart and blood vessels. • Sympathetic activation increases heart rate, inotropy, and dromotropy through the release of norepinephrine, which binds primarily to postjunctional cardiac ␤ 1 -adrenoceptors. Norepinephrine released by sympathetic nerves constricts blood vessels by binding to postjunctional ␣ 1 and ␣ 2 - adrenoceptors. The release of norepinephrine from sympathetic nerve terminals is modulated by prejunctional ␣ 2 -adrenoceptors, ␤ 2 -adrenoceptors and muscarinic (M 2 ) receptors. • Parasympathetic activation decreases heart rate, inotropy, and dromotropy, and it produces vasodilation in specific organs through the release of acetylcholine, which binds to postjunctional muscarinic (M 2 ) receptors. • Baroreceptors are mechanoreceptors that respond to stretch induced by an increase in pressure or volume. Arterial baroreceptor activity (e.g., carotid sinus and aortic arch receptors) tonically inhibits sympathetic outflow to the heart and blood vessels, and it tonically stimulates vagal outflow to the heart. Decreased arterial pressure, therefore, decreases the firing of arterial baroreceptors, which leads to reflex activation of sympathetic influences acting on the heart and blood vessels and with- drawal of the vagal activity to the heart. • Peripheral chemoreceptors (e.g., carotid bodies) and central chemoreceptors (e.g., medullary chemoreceptors) respond to decreased pO 2 and pH or increased pCO 2 of the blood. Their primarily function is to regulate respiratory activity, although NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION 137 TABLE 6-4 EFFECTS OF NEUROHUMORAL ACTIVATION ON BLOOD VOLUME, CARDIAC OUTPUT AND ARTERIAL PRESSURE INCREASED BLOOD VOLUME CARDIAC OUTPUT ARTERIAL PRESSURE Sympathetic Activity ↑↑ ↑ Vagal Activity — ↓↓ Circulating Epinephrine ↑↑↓↑* Angiotensin II ↑↑ ↑ Aldosterone ↑↑ ↑ Atrial Natriuretic Peptide ↓↓ ↓ Arginine Vasopressin ↑↑ ↑ ↑ = increase; ↓ = decrease. *dependent upon plasma epinephrine concentration. Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 137 chemoreceptor activation generally leads to activation of the sympathetic nervous system to the vasculature, which increases arterial pressure. Heart rate responses depend upon changes in respiratory activity. • Reflexes triggered by changes in blood volume, cerebral and myocardial ischemia, pain, pulmonary activity, muscle and joint movement, and temperature alter cardiac and vascular function. • Sympathetic activation of the adrenal medulla stimulates the release of catecholamines, principally epinephrine. This hormone produces cardiac stimulation (via ␤ 1 -adrenoceptors), and it either decreases (via vascular ␤ 2 -adrenoceptors) or increases (via vascular ␣ 1 and ␣ 2 -adrenoceptors) systemic vascular resistance, depend- ing upon the plasma concentration. • The renin-angiotensin-aldosterone system plays a major role in regulating renal excre- tion of sodium and water, and therefore it strongly influences blood pressure through changes in blood volume. Renin is released by the kidneys in response to sympathetic stimulation, hypotension, and decreased sodium delivery to distal tubules. Renin acts upon angiotensinogen to form angiotensin I, which is converted to angiotensin II (AII) by angiotensin-converting enzyme (ACE). AII has the following actions: (1) it stimulates aldosterone release from the adrenal cortex, which increases renal sodium reabsorption; (2) it acts on renal tubules to increase sodium reabsorption; (3) it stimulates thirst; (4) it produces systemic vasoconstriction; (5) it enhances sympathetic activity; and (6) it produces cardiac and vascular hypertrophy. The overall systemic effect of increased AII is increased blood volume, venous pressure, and arterial pressure. • Atrial natriuretic peptide (ANP), which is released by the atria primarily in response to atrial stretch, functions as a counter-regulatory mechanism for the renin-angiotensin-aldosterone system. Therefore, increased ANP reduces blood volume, venous pressure, and arterial pressure. • Arginine vasopressin (AVP; antidiuretic hormone), which is released by the posterior pituitary when the body needs to reduce renal loss of water, enhances blood volume and increases arterial and venous pressures. At high plasma concentrations, AVP constricts resistance vessels. Review Questions Please refer to the appendix for the answers to the review questions. For each question, choose the one best answer: 1. The cell bodies for the preganglionic vagal efferents innervating the heart are found in which region of the brain? a. Cortex b. Hypothalamus c. Medulla d. Nucleus tractus solitarius 2. Norepinephrine released by sympathetic nerves a. Binds preferentially to ␤ 2 -adrenoceptors on cardiac myocytes. b. Constricts blood vessels by binding to ␣ 1 -adrenoceptors. c. Inhibits its own release by binding to prejunctional ␤ 2 -adrenoceptors. d. Decreases renin release in the kidneys. 3. Stimulating efferent fibers of the right vagus nerve a. Decreases systemic vascular resistance. b. Increases atrial inotropy. c. Increases heart rate. d. Releases acetylcholine, which binds to M 2 receptors. 4. A sudden increase in carotid artery pressure a. Decreases carotid sinus baroreceptor firing rate. b. Increases sympathetic efferent nerve activity to systemic circulation. c. Increases vagal efferent activity to the heart. d. Results in reflex tachycardia. 138 CHAPTER 6 Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 138 5. Which of the following can cause tachycardia? a. Face submersion in cold water b. Increased blood pCO 2 c. Increased firing of carotid sinus baroreceptors d. Vasovagal reflex 6. Infusion of a low-to-moderate dose of epinephrine following pharmacologic blockade of ␤-adrenoceptors will a. Decrease mean arterial pressure. b. Have no significant cardiovascular effects. c. Increase heart rate. d. Increase systemic vascular resistance. 7. In an experimental protocol, intravenous infusion of acetylcholine was found to decrease mean arterial pressure and increase heart rate. These results can best be ex- plained by a. Direct action of acetylcholine on muscarinic receptors at the sinoatrial node. b. Increased firing of carotid sinus baroreceptors. c. Reflex activation of sympathetic nerves. d. Reflex systemic vasodilation. 8. An increase in circulating angiotensin II concentrations a. Depresses sympathetic activity. b. Increases blood volume. c. Inhibits aldosterone release. d. Inhibits the release of atrial natriuretic peptide. 9. Atrial natriuretic peptide a. Enhances renal sodium retention. b. Increases renin release. c. Inhibits the release of aldosterone. d. Increases blood volume and cardiac output. SUGGESTED READINGS Berne RM, Levy MN. Cardiovascular Physiology. 8th Ed. Philadelphia: Mosby, 2001. Melo LG, Pang SC, Ackermann U. Atrial natriuretic peptide: regulator of chronic arterial blood pressure. News Physiol Sci 2000;15:143–149. Mendolowitz D. Advances in parasympathetic control of heart rate and cardiac function. News Physiol Sci 1999;14:155–161. Rhoades RA, Tanner GA. Medical Physiology. 2nd Ed. Philadelphia: Lippincott Williams & Wilkins, 2003. Touyz CB, Dominiczak AF, Webb RC, Johns DB. Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide. Am J Physiol 2001;281:H2337–H2365. NEUROHUMORAL CONTROL OF THE HEART AND CIRCULATION 139 Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 139 Ch06_117-140_Klabunde 4/21/04 11:26 AM Page 140 [...]... from the left panel The autoregulatory range is the range of pressures over which flow shows little change Below or above the autoregulatory range, flow changes are approximately proportional to the changes in perfusion pressure The autoregulatory range as well as the flatness of the autoregulatory response curve varies among organs Fig 7-3 ), the upper limit of the autoregulatory range is reached and the. .. found to decrease during cardiac systole and increase during diastole (Fig 7-7 ) Therefore, most of the blood flow to the myocardium occurs during diastole The reason that coronary flow is influenced by the cardiac cycle is that during systole, the contraction of the myocardium compresses the microvasculature within the ventricular wall, thereby increasing resistance and decreasing flow During systole,... autoregulation occur, and why is it important? In hypotension caused by blood loss, despite baroreceptor reflexes that lead to constriction of much of the systemic vasculature, blood flow to the brain and myocardium will not decline appreciably (unless the arterial pressure falls below the autoregulatory range) This is because of the strong capacity of these organs to autoregulate and their ability to. .. endothelial and vascular damage, disruption of the blood-brain barrier, and hemorrhagic stroke With chronic hypertension, the autoregulatory curve shifts to the right (see Fig 7-1 1), which helps to protect the brain at higher arterial pressures However, this rightward shift then makes the brain more susceptible to reduced perfusion when arterial pressure falls below the lower end of the rightward-shifted... (␣1-adrenoceptor mediated) followed by vasodilation The vasodilation occurs because sympathetic activation of the heart also increases heart rate and inotropy through ␤1-adrenoceptors, which leads to the production of vasodilator metabolites that inhibit the vasoconstrictor response and cause vasodilation This is termed functional sympatholysis If ␤1-adrenoceptors are blocked experimentally, sympathetic... decreased With autoregulation (red line), the initial fall in pressure leads to a decrease in vascular resistance, which causes flow to increase to a new steady-state level despite the reduced perfusion pressure (point B) The right panel shows steady-state, autoregulatory flows plotted against different perfusion pressures Points A and B represent the control flow and autoregulatory steady-state flow, respectively,... autoregulate and their ability to escape sympathetic vasoconstrictor influences The autoregulatory response helps to ensure that these critical organs have an adequate blood flow and oxygen delivery even in the presence of systemic hypotension Other situations occur in which systemic arterial pressure does not change, but in which autoregulation is very important nevertheless Autoregulation can occur when a distributing... response helps to maintain normal blood flow in the presence of upstream stenosis, and it is particularly important in organs such as the brain and heart in which partial occlusion of large arteries can lead to significant reductions Ch07_14 1-1 70_Klabunde 4/21/04 11:43 AM Page 150 CHAPTER 7 vascular tone and thereby return flow to normal levels The longer the period of occlusion, the greater the metabolic... 4) Second, tachycardia further impairs coronary perfusion because the duration of diastole relative to systole decreases at elevated heart rates This reduces the time available for coronary perfusion during diastole, which is the time when the greatest amount of coronary perfusion occurs It is common in clinical practice to give either a ␤-blocker or calcium-channel blocker to a patient with both coronary... Hypertension Acute Sympathetic Stimulation 0 100 200 Perfusion Pressure (mm Hg) FIGURE 7-1 1 Autoregulation of cerebral blood flow Cerebral blood flow shows excellent autoregulation between mean arterial pressures of 60 mm Hg and 130 mm Hg The autoregulatory curve shifts to the right with chronic hypertension or acute sympathetic activation This shift helps to protect the brain from the damaging effects . the autoregulatory range). This is because of the strong capacity of these organs to autoregulate and their ability to escape sympathetic vasoconstrictor influences. The autoregulatory response. ␤ 2 -adrenoceptors) or increases (via vascular ␣ 1 and ␣ 2 -adrenoceptors) systemic vascular resistance, depend- ing upon the plasma concentration. • The renin-angiotensin-aldosterone system plays. baroreceptor activity (e.g., carotid sinus and aortic arch receptors) tonically inhibits sympathetic outflow to the heart and blood vessels, and it tonically stimulates vagal outflow to the

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