V2 RECEPTOR-MEDIATED VASODILATION IN HEALTHY HUMANS

Arginine vasopressin (AVP) causes biphasic changes in vascular resista nce in human forearms: vasoconstriction at lower doses and vasodilatio n at higher doses. Vasoconstriction is mediated by the V1 receptor, bu t the mechanism of AVP-induced vasodilation remains unclear. To determ ine if the AVP-induced vasodilation in human forearm vessels is mediat ed by the V2 receptor, we examined the effects of OPC-31260 (a novel v asopressin V2 receptor antagonist) on AVP-induced vasodilation. The br achial artery was cannulated for drug infusions and direct measurement of arterial blood pressure (BP). We measured forearm blood flow (FBF) by a strain-gauge plethysmograph and calculated forearm vascular resi stance (FVR). AVP was infused intraarterially (i.a.) at doses of 0.1, 0.2, 0.5, 1.0, and 2.0 ng/kg/min (n = 8). The lower dose of AVP (0.1 n g/kg/min) increased, whereas the higher doses of AVP (greater than or equal to 0.5 ng/kg/min) decreased, FVR (p < 0.01). Infusion of nitrogl ycerin (NTG) i.v. doses of 1.7, 3.3, and 10.0 ng/kg/min decreased FVR dose dependently (p < 0.01). OPC-31260(1.0 mu g/kg/min) infused i.a. d id not alter arteral BP, baseline FVR, or heart rate (HR). OPC-31260 d id not affect AVP-induced vasoconstriction but blocked AVP-induced vas odilation completely. OPC-31260 did not affect NTG-induced vasodilatio n. These results suggest that AVP-induced vasodilation is mediated by the V2 receptor in human forearm resistance vessels.