Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats

The aim of the present study was to determine the receptor subtype involved in arginine vasopressin (AVP)-induced modulation of baroreflex function in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel nonpeptide AVP V-1- and V-2-receptor antagonists. Baroreceptor heart rate (HR) reflex was investigated in both SHR and WKY rats which were intravenously administered the selective V-1- and V-2-receptor antagonists OPC-21268 and OPC-31260, respectively. Baroreflex function was assessed by obtaining alternate presser and depressor responses to phenylephrine and sodium nitroprusside, respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex activity was tested before and after intravenous administration of vehicle (20% DMSO), OPC-21268 (10 mg/kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not significantly alter basal mean arterial pressure (MAP) and HR values or baroreflex function in SHR or WKY rats. The V-1-receptor antagonist had no significant effect on resting MAP or HR values or on baroreflex parameters in both groups of rats, although this dose was shown to significantly inhibit the presser response to AVP (5 ng iv; ANOVA, P < 0.05). In SHR but not WKY rats the V-2-receptor antagonist significantly attenuated the gain (or slope) of the baroreflex curve (to 73 +/- 3 and 79 +/- 7% of control for 1 and 10 mg/kg, respectively), although AVP-induced presser responses were also attenuated with the higher dose of the V-2-receptor antagonist. These findings suggest that AVP tonically enhances baroreflex function through a V-2 receptor in the SHR.