V2 receptor-mediated vasodilation in healthy humans

Area of Science:

• Cardiovascular Physiology
• Pharmacology

Background:

• Arginine vasopressin (AVP) exhibits dose-dependent biphasic effects on human forearm vascular resistance, causing vasoconstriction at low doses and vasodilation at high doses.
• While V1 receptors mediate AVP-induced vasoconstriction, the mechanism underlying AVP-mediated vasodilation remains elusive.

Purpose of the Study:

• To investigate whether the V2 receptor mediates AVP-induced vasodilation in human forearm vasculature.
• To assess the efficacy of OPC-31260, a selective V2 receptor antagonist, in blocking AVP-induced vasodilation.

Main Methods:

• Intra-arterial infusions of AVP were administered to human subjects at varying doses (0.1-2.0 ng/kg/min) to measure forearm blood flow (FBF) and forearm vascular resistance (FVR).
• The effects of OPC-31260 on AVP-induced changes in FVR and vasodilation induced by nitroglycerin (NTG) were evaluated.
• Arterial blood pressure (BP) and heart rate (HR) were monitored throughout the study.

Main Results:

• AVP induced vasoconstriction at lower doses and vasodilation at higher doses, significantly altering FVR (p < 0.01).
• OPC-31260 administration did not affect baseline BP, FVR, or HR, nor did it alter AVP-induced vasoconstriction.
• Crucially, OPC-31260 completely blocked AVP-induced vasodilation without affecting NTG-induced vasodilation.

Conclusions:

• The findings strongly suggest that AVP-induced vasodilation in human forearm resistance vessels is primarily mediated by the V2 receptor.
• OPC-31260 serves as a specific antagonist for the V2 receptor, effectively inhibiting AVP-mediated vasodilation.