Vasopressin Volume receptor

Stmctural defects at the receptor level are determinant for a number of receptor diseases. In nephrogenic diabetes insipidus, where patients void large volumes of dilute urine even in the presence of vasopressin (antidiuretic hormone) (105), the disease is linked to mutations in three discrete regions of the G-protein-linked vasopressin (V2) receptor (106,107). 

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. 

Although the regulation of the secretion of vasopressin appeared simple a few decades ago and seemed to involve only the activation of the osmoreceptor, it is now clear that a number of factors not related to osmolarity also regulate vasopressin secretion. They include blood volume receptors, systemic barorecep-tors and hormones such as catecholamine, prostaglandins, adrenocortical hormones, thyroid hormones, and the renin-angiotensin system. 

Changes in blood volume are sensed by an intratho-racic volume receptor which stimulates vasopressin secretion. The most direct evidence for the existence of a volume receptor was obtained by distending the left atrium, an operation that leads to increased diuresis. Vagotomy abolishes the diuretic response to atrial distension. Increased atrial pressure can also be produced in anesthetized dogs by atrial pacing. This is normally accompanied by increased diuresis. Both va-... 

It is not known how the volume receptor and the baroreceptor interact to regulate the secretion of vasopressin. 

Inhibition of V2 vasopressin receptors causes an increase in urine volume primarily by reducing the re-absoiption of water along the collecting duct, an aquaretic effect that is fundamentally different from the natriuretic actions discussed so far. Nevertheless, some of the conditions calling for the use of natriuretic intervention are identical to those in which the administration of a new class of orally active nonpeptide V2 antagonists may be useful (tolvaptan, lixivaptan, and others). 

The most important stimulus to the release of ANP from the heart is atrial stretch via mechanosensitive ion channels. ANP release is also increased by volume expansion, changing from the standing to the supine position, and exercise. ANP release can also be increased by sympathetic stimulation via aiA-adrenoceptors, endothelins via the -receptor subtype (see below), glucocorticoids, and vasopressin. Plasma ANP concentration increases in various pathologic states, including heart failure, primary aldosteronism, chronic renal failure, and inappropriate ADH secretion syndrome. 

Shuaib A, Xu WC, Yang T, Noor R (2002) Effects of nonpeptide V( 1) vasopressin receptor antagonist SR-49059 on infarction volume and recovery of ftmction in a focal embolic stroke model. Stroke 33 3033-3037... 

Besides the osmoreceptor mechanism of vasopressin release, the physiological regulation of vasopressin secretion also involves a pressure-volume mechanism that is distinct from the osmotic sensor. AVP release is regulated by baro-receptors that respond to alterations in blood volume. For example, a reduction in plasma volume or arterial pressure,... 

OTHER WATER-RETAINING STATES In patients with congestive heart failure, cirrhosis, or nephrotic syndrome, ejfective blood volume often is reduced, and hypovolemia frequently is exacerbated by the liberal use of diuretics. Since hypovolemia stimulates vasopressin release, patients may become hyponatremic owing to vasopressin-mediated retention of water. The development of potent orally active receptor antagonists and specific inhibitors of water chaimels in the collecting duct would provide an effective therapeutic strategy not only in patients with SIADH but also in the much more common setting of hyponatremia in patients with heart faftme, cirrhosis, or nephrotic syndrome. 

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