Arterial baroreceptors

Many different types of sensory receptors are located throughout the body. These receptors monitor the status of the internal environment or that of the surroundings. Sensory receptors are sensitive to specific types of stimuli and measure the value of a physiological variable. For example, arterial baroreceptors measure blood pressure and chemoreceptors measure the oxygen and carbon dioxide content of the blood. The information detected by these sensors then travels by way of afferent neuronal pathways to the central nervous system (CNS). The CNS is the integrative portion of the nervous system and consists of the (1) brain and the (2) spinal cord. 

Besides the arterial baroreceptors, central projections from other inputs, for example cardiac mecha-no-receptors, chemo-receptors, pulmonary stretch receptors, and somatic inputs, are capable of influencing the controlling system and thereby the autonomic effectors. 

The short-term mechanism controlling BP from minute to minute involves arterial baroreceptors. When changing body position, baroreceptors detect changes in BP and elicit reflex responses via the cardiovascular centre in the medulla, which reverse the change and return BP to the original level. Baroreceptors operate these reflexes in hypertension, but adapt to the increased pressure so that they operate around a higher set point. 

Baroreflex sensitivity (BRS) is a measure of the reflex bradycardia that follows an increase in systemic blood pressure. This reflex is mediated by arterial baroreceptors and may be measured after injection of phenylephrine or after spontaneous rises in blood pressure (64). Correlation between the two different tests is poor (69) and measures of baroreflex sensitivity are only moderately reproducible (70). Data on the ability of BRS to predict sudden death are conflicting. In the ATRAMI study in 1284 patients post-MI, HRV, and BRS were assessed at discharge (71). Depressed HRV and BRS carried a significant risk of cardiac mortality when both parameters were depressed the risk increased further. Thus, ATRAMI demonstrated that since BRS adds to the prognostic value of HRV, the two measures are complimentary rather than redundant. However, in another study of 700 post-MI patients, HRV or BRS was not predictive of SCD (60). BRS also does not appear useful for risk stratification in patients with nonischemic cardiomyopathy (63). 

Czyzyk-Krzeska MF, Bayliss DA, Lawson EE, Millhom DE. Expression of messenger RNAs for peptides and tyrosine hydroxylase in primary sensory neurons that innervate arterial baroreceptors and chemoreceptors. Neurosci Lett 1991 129 98-102. Dahlstrom A, Fuxe K. Evidence for the existence of monoamine containing neurons in the central nervous system. I. Demonstration of monoamines in the cell bodies of brainstem neurons. Acta Physiol Scand 1964 62 1-55. 

Baroreceptor. Specialized pressure-sensitive tissue located in carotid arteries. Nerve impulses proportional to arterial blood pressure are conducted from this tissue to the brain which in turn exerts control over the blood pressure. 

The baroreceptor reflex is a central reflex mechanism, which reduces heart rate following an increase in blood pressure. Each change in blood pressure is sensed by baroreceptors in the carotid arteries, which activate the autonomic nervous system to alter heart rate and thereby readjust blood pressure. 

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. 

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

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. 

Low-pressure receptors. The low-pressure receptors are located in the walls of the atria and the pulmonary arteries. Similar to baroreceptors, low-pressure receptors are also stretch receptors however, stimulation of these receptors is caused by changes in blood volume in these low-pressure areas. An overall increase in blood volume results in an increase in venous return an increase in the blood volume in the atria and the pulmonary arteries and stimulation of the low-pressure receptors. These receptors then elicit reflexes by way of the vasomotor center that parallel those of baroreceptors. Because an increase in blood volume will initially increase MAP, sympathetic discharge decreases and parasympathetic discharge increases so that MAP decreases toward its normal value. The simultaneous activity of baroreceptors and low-pressure receptors makes the total reflex system more effective in the control of MAP. 

A more moderate stimulus for thirst and ADH secretion is a decrease in extracellular fluid, or plasma volume. This stimulus involves low-pressure receptors in the atria of the heart as well as baroreceptors in the large arteries. A decrease in plasma volume leads to a decrease in atrial filling, which is detected by low-pressure receptors, and a decrease in MAP, which the baroreceptors detect. Each of these receptors then provides excitatory inputs to the thirst center and to the ADH-secreting cells. 

All patients taking these drugs for long-term hypertension therapy should first receive both a diuretic and a /1-blocker. The diuretic minimizes the side effect of sodium and water retention. Direct vasodilators can precipitate angina in patients with underlying coronary artery disease unless the baroreceptor reflex mechanism is completely blocked with a /3-blocker. Nondihydropyridine CCBs can be used as an alternative to /3-blockers in patients with contraindications to /3-blockers. 

The development of ascites is related to systemic arterial vasodilation that leads to the activation of the baroreceptors in the kidney and an activation of the renin-angiotensin system, with sodium and water retention and vasoconstrictor production. 

There is another system involved in blood pressure regulation the renin-angiotensin-aldosterone system (Fig. 2). The arterial blood pressure in the kidney influences intrarenal baroreceptors which together with the sodium load at the macula densa lead to renin liberation, angiotensin formation and aldosterone secretion, which by influencing the sodium balance changes the blood volume and influences the arterial blood pressure. 

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. 

Arterial blood pressure (afterload) is also reduced by propranolol. Although the mechanisms responsible for this antihypertensive effect are not completely understood, they are thought to involve (1) a reduction in cardiac output, (2) a decrease in plasma renin activity, (3) an action in the central nervous system, and (4) a resetting of the baroreceptors. Thus, propranolol may exert a part of its benehcial effects in secondary angina by decreasing three of the major determinants of myocardial oxygen demand, that is, heart rate, contractihty, and systolic wall tension. 

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. 

Arterioles relax less than venules because GTN evokes reflexes by baroreceptors which respond to decreased arterial pressure leading to reflex sympathetic discharge causing tachycardia and increased cardiac contractility. 

Unlike isoflurane, desflurane may stimulate the sympathetic nervous system at concentrations above 1 MAC. Sudden and unexpected increases in arterial blood pressure and heart rate have been reported in some patients, accompanied by increases in plasma catecholamine and vasopressin concentrations and increased plasma renin activity. These pressor effects may increase morbidity or mortality in susceptible patients. The mechanism of sympathetic activation is unclear but does not appear to be baroreceptor-mediated. Clonidine, esmolol, fentanyl and propofol partially block the response but lignocaine (lignocaine) is ineffective. 

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. 

The indirect effects of nitroglycerin consist of those compensatory responses evoked by baroreceptors and hormonal mechanisms responding to decreased arterial pressure (see Figure 6-7) this often results in tachycardia and increased cardiac contractility. Retention of salt and water may also be significant, especially with intermediate- and long-acting nitrates. These compensatory responses contribute to the development of tolerance. 

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... 

Vasopressin also plays an important role in the short-term regulation of arterial pressure by its vasoconstrictor action. It increases total peripheral resistance when infused in doses less than those required to produce maximum urine concentration. Such doses do not normally increase arterial pressure because the vasopressor activity of the peptide is buffered by a reflex decrease in cardiac output. When the influence of this reflex is removed, eg, in shock, pressor sensitivity to vasopressin is greatly increased. Pressor sensitivity to vasopressin is also enhanced in patients with idiopathic orthostatic hypotension. Higher doses of vasopressin increase blood pressure even when baroreceptor reflexes are intact. 

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