Receptor baroreceptors

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. 

Logically, ADH receptor antagonists, and ADH synthesis and release inhibitors can be effective aquaretics. ADH, 8-arginine vasopressin [113-79-17, is synthesized in the hypothalamus of the brain, and is transported through the supraopticohypophyseal tract to the posterior pituitary where it is stored. Upon sensing an increase of plasma osmolaUty by brain osmoreceptors or a decrease of blood volume or blood pressure detected by the baroreceptors and volume receptors, ADH is released into the blood circulation it activates vasopressin receptors in blood vessels to raise blood pressure, and vasopressin V2 receptors of the nephrons of the kidney to retain water and electrolytes to expand the blood volume. 

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

Cardiovascular-peripheral vasodilation,decreased peripheral resistance, inhibition of baroreceptors (pressure receptors located in the aortic arch and carotid sinus that regulate blood pressure), orthostatic hypotension and fainting... 

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. 

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. 

It is important to note that the baroreceptor reflex is elicited whether blood pressure increases or decreases. Furthermore, these receptors are... 

Figure 15.6 The baroreceptor reflex. Baroreceptors are the most important source of input to the vasomotor center. The reflex elicited by these receptors is essential in maintenance of normal blood pressure.

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. 

Baroreceptors are sensitive to changes in MAP. As VR, CO, and MAP decrease, baroreceptor excitation is diminished. Consequently, the frequency of nerve impulses transmitted from these receptors to the vasomotor center in the brainstem is reduced. This elicits a reflex that will increase HR, increase contractility of the heart, and cause vasoconstriction of arterioles and veins. The increase in CO and TPR effectively increases MAP and therefore cerebral blood flow. Constriction of the veins assists in forcing blood toward the heart and enhances venous return. Skeletal muscle activity associated with simply walking decreases venous pressure in the lower extremities significantly. Contraction of the skeletal muscles in the legs compresses the veins and blood is forced toward the heart. 

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. 

A pathologic disturbance in the CNS, autonomic nerve fibers, adrenergic receptors, or baroreceptors ... 

Clonidine, guanabenz, guanfacine, and methyldopa lower BP primarily by stimulating a2-adrenergic receptors in the brain, which reduces sympathetic outflow from the vasomotor center and increases vagal tone. Stimulation of presynaptic oq-receptors peripherally may contribute to the reduction in sympathetic tone. Consequently, there may be decreases in heart rate, cardiac output, total peripheral resistance, plasma renin activity, and baroreceptor reflexes. 

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. 

Three generally accepted mechanisms are involved in the regulation of renin secretion (Fig. 18.2). The first depends on renal afferent arterioles that act as stretch receptors or baroreceptors. Increased intravascular pressure and increased volume in the afferent arteriole inhibits the release of renin. The second mechanism is the result of changes in the amount of filtered sodium that reaches the macula densa of the distal tubule. Plasma renin activity correlates inversely with dietary sodium intake. The third renin secretory control mechanism is neurogenic and involves the dense sympathetic... 

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. 

Thus, studies of clonidine and methyldopa suggest that normal regulation of blood pressure involves central adrenergic neurons that modulate baroreceptor reflexes. Clonidine and a-methylnorepinephrine bind more tightly to a2 than to adrenoceptors. As noted in Chapter 6, a2 receptors are located on presynaptic adrenergic neurons as well as some postsynaptic sites. It is possible that clonidine and -methylnorepinephrine act in the brain to reduce norepinephrine release onto relevant receptor sites. Alternatively, these drugs may act on postsynaptic a2 adrenoceptors to inhibit activity of appropriate neurons. Finally, clonidine also binds to a nonadrenoceptor site, the imidazoline receptor, which may also mediate antihypertensive effects. 

Pathophysiology In HF patients, the levels of aldosterone are elevated, even in the presence of ACE inhibitors or angiotensin-receptor blockers (34,35). Aldosterone has detrimental effects in HE such as causing potassium and magnesium loss, sodium retention, baroreceptor dysfunction, and myocardial fibrosis it also decreases the neuronal uptake... 

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. 

In contrast to phenoxybenzamine, phentolamine [fen TOLE a meen] produces a competitive block of ai and a2 receptors. The drug s action lasts for approximately 4 hours after a single administration. Like phenoxybenzamine, it produces postural hypotension and causes epinephrine reversal. Phentolamine had been used in the diagnosis of pheochromocytoma and in other clinical situations associated with excess release of catecholamines. Phentolamine-induced reflex cardiac stimulation and tachycardia are mediated by the baroreceptor reflex and by blocking the a2 receptors of the cardiac sympathetic nerves. The drug can also trigger arrhythmias and anginal pain and is contraindicated in patients with decreased coronary perfusion. 

Increased sympathetic activity Baroreceptors sense a decrease in blood pressure, and trigger activation of p-adrenergic receptors in the heart. This results in an increase in heart rate and a greater force of contraction of the heart muscle (Figure 16.4). In addition, vasoconstriction (ai-mediated) enhances venous return and increases cardiac preload. These compensatory responses increase the work of the heart and, therefore, can contribute to the further decline in cardiac function. 

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