Neurohypophysial hormones.

THE ACTIONS OF ANTIDIURETIC hormone or vasopressin (AVP) to promote water retention and to acutely increase arterial pressure are well established. Oxytocin (OT) has well known effects on uterine contraction and milk ejection. In addition to these widely recognized hormonal actions, these peptides have additional behavioral, autonomic, renal, and cardiovascular effects, the physiological significance of which has been a topic of considerable interest to the authors contributing to this journal. AVP is a potent vasoconstrictor, but it is also capable of producing vasodilation. The vasoconstrictor effects of AVP are mediated via activation of V1 receptors; V2 receptors mediate the vasodilatory effects of the hormone, as well as its antidiuretic actions. Usually, the vasoconstrictor effects of AVP predominate, which is the basis for its role in the acute regulation of arterial pressure. For example, infant rats respond to moderate cold exposure with increased heat production by brown adipose tissue (5). However, at greater thermal challenges, thermogenesis can no longer compensate for heat loss, leading to substantial bodily cooling and bradycardia. In response to the resultant decrease in cardiac output, maintenance of arterial pressure is dependent on an increase in peripheral resistance, which is due, in part, to the vasoconstrictor effects of AVP (5). An impaired vasoconstrictor response to AVP appears to contribute to systemic vasodilation and hypotension in septic shock (6). In septic shock, the diminished vasoconstrictor response to AVP is due to downregulation of V1 receptors, a response that is likely mediated by proinflammatory cytokines. The vasodilatory effects of AVP are most readily exposed after V1 receptor antagonist administration, particularly when sympathetic reflexes are impaired. After V1 receptor blockade, incremental infusions of AVP caused progressive and comparable reductions in peripheral resistance in normal and quadriplegic subjects (9). However, arterial pressure decreased only in the latter, despite much larger compensatory increases in PRA, because of deficient reflex-mediated increments in cardiac output. At least in rats, hypotension stimulates the secretion of OT, as well as AVP. During hypotension, OT contributes to the maintenance of arterial pressure by stimulating renin release (15). Both AVP and OT have actions at the central nervous system that impact cardiovascular function. These actions are a result of the secretion of these peptides from oxytocinergic and vasopressinergic projections within the nervous system, as well as the secretion of these neurohypophysial hormones from magnocellular neurons, which, via the circulation, activate receptors at circumventricular organs. OT projections from parvocellular neurons of the paraventricular nucleus (PVN) to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia and facilitate baroreflex-mediated bradycardia in response to increased arterial pressure (14). OT released at the lumbosacral spinal cord by descending projections from the parvocellular PVN activates proerectile neurons and, therefore, plays a role in reproductive function (12). The central actions of AVP (V1 receptor response) account for postexercise reductions in arterial pressure and heart rate, possibly by enhancing baroreflex function by activating receptors in the area postrema that project to the nucleus of the solitary tract (8). AVP is also released during stress and contributes, along with corticotropin-releasing hormone (CRH), to increased ACTH secretion (17). This presumably occurs in two ways. First, the AVP that is coreleased with CRH into the primary capillaries of the portal circulation in the stalk-median eminence region directly stimulates ACTH producing anterior pituitary cells. Second, the circulating AVP secreted from magnocellular neurons acts at the hypothalamus to increase the synthesis and release of CRH. There has been considerable interest in the neurohormonal mechanisms that influence salt appetite (1, 10, 24, 25, 29). The diversity of experimental models (e.g., adrenalectomy, dietary sodium deprivation, hypovolemia, fluid deprivation) used to evoke salt appetite undoubtedly results in different alterations in body fluid volumes, blood pressure, and neurohormonal responses, all of which must be carefully considered in the interpretation of experimental findings. In rats purportedly sodium depleted by administration of furosemide and DOCA, central administration of an antagonist to the AVP-V1 (but not the AVP-V2) receptor suppressed salt appetite, implicating a central role for this peptide in stimulating salt intake (10). In contrast, Schoorlemmer et al. (25) concluded that circulating ANG II, but not circulating AVP, accounts for most of the sodium appetite in adrenalectomized rats. In another study, mice in which the gene for OT had been deleted were given the choice between hypertonic saline and tap water after overnight fluid deprivation (1). Compared with wild-type, OT-deficient mice ingested considerably greater amounts of saline, supporting an inhibitory role for OT in the control of sodium appetite in this model. Further support for an inhibitory role of OT in salt appetite was provided by Roesch et al. (24), who were cognizant of the fact that OT limits the Address for reprint requests and other correspondence: T. E. Lohmeier, Univ. of Mississippi Medical Center, 2500 North State St., Jackson, MS 39216-4505 (E-mail: [email protected]). Am J Physiol Regul Integr Comp Physiol 285: R715–R717, 2003; 10.1152/ajpregu.00390.2003.