Regulation of plasma vasopressin and renin activity in conscious hindlimb-unloaded rats

Cardiovascular deconditioning occurs in astronauts after spaceflight or in individuals subjected to bed rest. It is characterized by an increased incidence of orthostatic intolerance. The mechanisms responsible for orthostatic intolerance are likely multifactorial and may include hypovolemia, autonomic dysfunction, and vascular and cardiac alterations. The arterial baroreflex is an important compensatory mechanism in the response to an orthostatic stress. In a previous study, we demonstrated that arterial baroreflex mediated sympathoexcitation was blunted in hindlimb-unloaded (HU) rats, a model of cardiovascular deconditioning. The arterial baroreflex also contributes to the regulation of vasoactive hormones including vasopressin and angiotensin II. In the present study, we tested the hypothesis that the neurohumoral response to hypotension is also attenuated in rats after 14 days of hindlimb unloading. To test this hypothesis, the vasodilator diazoxide (15 or 25 mg/kg) or saline (0.9%) was administered to produce hypotension or control conditions, respectively, in conscious HU and control rats. Plasma samples were collected and assayed for vasopressin and plasma renin activity (PRA). Diazoxide (25 mg/kg) produced significant increases in vasopressin and PRA compared with saline controls. HU rats exhibited significantly higher levels of vasopressin at rest and the increase in vasopressin levels during hypotension was enhanced by hindlimb unloading. Neither resting nor hypotension-induced PRA was altered by hindlimb unloading. These data suggest that although baroreflex-mediated sympathoexcitation is blunted by hindlimb unloading, hypotension-induced vasopressin release is enhanced and hypotension-induced PRA is unaffected. Increased circulating vasopressin may serve to compensate for blunted baroreflex regulation of sympathetic nervous activity produced by hindlimb unloading or may actually contribute to it.