Vascular baroreceptors

An example of this type of reflex is the baroreceptor reflex (see Figure 1.2). Baroreceptors located in some of the major systemic arteries are sensory receptors that monitor blood pressure. If blood pressure decreases, the number of sensory impulses sent from the baroreceptors to the cardiovascular control center in the brainstem also decreases. As a result of this change in baroreceptor stimulation and sensory input to the brainstem, ANS discharge to the heart and blood vessels is adjusted to increase heart rate and vascular resistance so that blood pressure increases to its normal value. 

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

A decrease in plasma volume leads to decreased MAP, which is detected by baroreceptors in the carotid sinuses and the arch of the aorta. By way of the vasomotor center, the baroreceptor reflex results in an overall increase in sympathetic nervous activity. This includes stimulation of the heart and vascular smooth muscle, which causes an increase in cardiac output and total peripheral resistance. These changes are responsible for the short-term regulation of blood pressure, which temporarily increases MAP toward normal. 

Any sudden alteration in the mean arterial blood pressure tends to produce compensatory reflex changes in heart rate, contractility, and vascular tone, which will oppose the initial pressure change and restore the homeostatic balance. The primary sensory mechanisms that detect changes in the mean arterial blood pressure are stretch receptors (baroreceptors) in the carotid sinus and aortic arch. 

The injection of a vasoconstrictor, which causes an increase in mean arterial blood pressure, results in activation of the baroreceptors and increased neural input to the cardiovascular centers in the medulla oblongata. The reflex compensation for the drug-induced hypertension includes an increase in parasympathetic nerve activity and a decrease in sympathetic nerve activity. This combined alteration in neural firing reduces cardiac rate and force and the tone of vascular smooth muscle. As a consequence of the altered neural control of both the heart and the blood vessels, the rise in blood pressure induced by the drug is opposed and blunted. 

Halothane administration can result in a marked reduction in arterial blood pressure that is due primarily to direct myocardial depression, which reduces cardiac output. The fall in pressure is not opposed by reflex sympathetic activation, however, since halothane also blunts baroreceptor and carotid reflexes. Systemic vascular resistance is unchanged, although blood flow to various tissues is redistributed. Halothane also sensitizes the heart to the arrhythmogenic effect of catecholamines. Thus, maintenance of the patient s blood pressure with epinephrine must be done cautiously. 

A slow intravenous injection of histamine produces marked vasodilation of the arterioles, capillaries, and venules. This causes a fall in blood pressure whose magnitude depends on the concentration of histamine injected, the degree of baroreceptor reflex compensation, and the extent of histamine-induced release of adrenal catecholamines. Vasodilation of cutaneous blood vessels reddens the skin of the face, while a throbbing headache can result from vasodilation of brain arterioles. Vasodilation is mediated through both Hj- and Hj-receptors on vascular smooth muscle. Stimulation of Hj-receptors produces a rapid and short-lived response, whereas stimulation of H2-receptors produces a more sustained response that is slower in onset. Stimulation of Hj-receptors on sympathetic nerve terminals inhibits the release of norepinephrine and its associated vasoconstriction. 

Chapter 12 contains additional discussion of vasodilators. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside and the nitrates also relax veins. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system (Figure 11-4), as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

Diuretics are the mainstay of heart failure management and are discussed in detail in Chapter 15. They have no direct effect on cardiac contractility their major mechanism of action in heart failure is to reduce venous pressure and ventricular preload. This results in reduction of salt and water retention and edema and its symptoms. The reduction of cardiac size, which leads to improved pump efficiency, is of major importance in systolic failure. Spironolactone and eplerenone, the aldosterone antagonist diuretics (see Chapter 15), have the additional benefit of decreasing morbidity and mortality in patients with severe heart failure who are also receiving ACE inhibitors and other standard therapy. One possible mechanism for this benefit lies in accumulating evidence that aldosterone may also cause myocardial and vascular fibrosis and baroreceptor dysfunction in addition to its renal effects. 

Octreotide increases systemic vascular resistance, and bradycardia may be a baroreceptor-induced response. Octreotide also has direct effects on the heart, the main effects being reduced heart rate, reduced myocardial contractility, and slowing of the propagation velocity along the cardiac conduction system. 

The primary side effects associated with vasodilators include headache, dizziness, hypotension, and orthostatic hypotension. These effects are all related to the tendency of these drugs to increase peripheral blood flow and decrease peripheral vascular resistance. Vasodilators may also cause reflex tachycardia in certain patients if the baroreceptor reflex increases heart rate in an attempt to maintain adequate blood pressure. 

In most cases, elevated blood pressure is associated with an overall increase in resistance to flow of blood through arterioles, while cardiac output is usually normal. Meticulous investigation of autonomic nervous system function, baroreceptor reflexes, the renin-angiotensin-aldosterone system, and the kidney has failed to identify a primary abnormality as the cause of increased peripheral vascular resistance in essential hypertension. 

Angiotensin II inhibitors lower blood pressure principally by decreasing peripheral vascular resistance. Cardiac output and heart rate are not significantly changed. Unlike direct vasodilators, these agents do not result in reflex sympathetic activation and can be used safely in persons with ischemic heart disease. The absence of reflex tachycardia may be due to downward resetting of the baroreceptors or to enhanced parasympathetic activity. 

Prazosin (see structure in Figure 12.2), the prototypic drug in this class, decreases peripheral vascular resistance in arterioles and veins by blocking alpha receptors on vascular smooth muscle. It does not decrease cardiac output. Because of this effect, patients taking prazosin are more prone ( 50 percent) to postural hypotension, particularly following the first dose. In some cases, the hypotension is so severe that the patient may lose consciousness. In an attempt to compensate, the baroreceptors may produce an accompanying tachycardia. 

Diazoxide is a direct vasodilator that acts on vascular smooth muscle to produce systemic vasodilatation. As a result there is baroreceptor-mediated activation of the sjm-pathetic nervous system and the renin-angiotensm system. 

The opioids are considered relahvely safe from a cardiovascular standpoint. Myocardial depression is minimal. Changes in heart rate are species dependent and usually manifest as a mild decrease in heart rate however, a significant increase in heart rate can be seen in horses, which is consistent with the central excitatory effect that often occurs. Opioids inhibit the baroreceptor reflex response to changes in blood pressure. Certain opioids may cause systemic vasodilatation, decreased peripheral vascular resistance and hypotension secondary to histamine release. Morphine and meperidine (pethidine) are the opioids most likely associated with this effect. This is typically seen after rapid i.v. administration, is dose dependent and does not result from mast cell... 

Nonosmotic release of ADH occurs when the effective arterial blood volume (EABV) decreases by approximately 5% to 10%. The EABV is the vascular component of the ECF that is responsible for organ perfusion. A change in the EABV promotes an afferent response from baroreceptors in the chest and neck and activation of the renin-angiotensin system, leading to synthesis of angiotensin 11. Angiotensin 11 then stimulates both nonosmotic release of ADH and thirst. The volume stimulus overrides osmotic inhibition of ADH release, and conservation of water fosters restoration of blood pressure and EABV at the expense of hypo-osmolality. 

ACh produces dilation of essentially all vascular beds, including those of the pulmonary and coronary vasculature the effect is mediated by stimulation of endothehal NO production. Vasodilation of coronary beds may be elicited by baroreceptor or chemoreceptor reflexes or by direct electrical stimulation of the vagus however, neither parasympathetic vasodilator nor sympathetic vasoconstrictor tone plays a major role in the regulation of coronary blood flow relative to the effects of local oxygen tension and autoregulatory metabohc factors such as adenosine. 

Hydralazine (apresoline) causes direct relaxation of arteriolar smooth muscle, possibly secondary to a fall in intracellular Ca concentrations. The drug does not dilate epicardial coronary arteries or relax venous smooth muscle. Hydralazine-induced vasodilation is associated with powerful stimulation of the sympathetic nervous system, likely due to baroreceptor-mediated reflexes, which results in increased heart rate and contractility, increased plasma renin activity, and fluid retention all of these effects counteract the antihypertensive effect of hydralazine. Although most of the sympathetic activity is due to a baroreceptor-mediated reflex, hydralazine may stimulate NE release from sympathetic nerve terminals and augment myocardial contractility directly. Most of hydralazine s effects are confined to the cardiovascular system the decrease in blood pressure after administration is associated with a selective decrease in vascular resistance in the coronary, cerebral, and renal circulations, with a smaller effect in skin and muscle. Because of preferential dilation of arterioles, postural hypotension is not common, and hydralazine lowers blood pressure equally in the supine and upright positions. 

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