V2 receptor-mediated vasodilation in healthy humans.
Arginine vasopressin (AVP) causes biphasic changes in vascular resistance in human forearms: vasoconstriction at lower doses and vasodilation at higher doses. Vasoconstriction is mediated by the V1 receptor, but the mechanism of AVP-induced vasodilation remains unclear. To determine if the AVP-induced vasodilation in human forearm vessels is mediated by the V2 receptor, we examined the effects of OPC-31260 (a novel vasopressin V2 receptor antagonist) on AVP-induced vasodilation. The brachial 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 resistance (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 ng/kg/min) increased, whereas the higher doses of AVP (> or = 0.5 ng/kg/min) decreased, FVR (p < 0.01). Infusion of nitroglycerin (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 micrograms/kg/min) infused i.a. did not alter arterial BP, baseline FVR, or heart rate (HR). OPC-31260 did not affect AVP-induced vasoconstriction but blocked AVP-induced vasodilation completely. OPC-31260 did not affect NTG-induced vasodilation. These results suggest that AVP-induced vasodilation is mediated by the V2 receptor in human forearm resistance vessels.
Tagawa
T
T
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Imaizumi
T
T
Shiramoto
M
M
Endo
T
T
Hironaga
K
K
Takeshita
A
A
D000328:Adult; D001552:Benzazepines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007269:Injections, Intra-Arterial; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology; D017483:Receptors, Vasopressin / Q000187:drug effects / Q000502:physiology*; D012039:Regional Blood Flow / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014667:Vasopressins / Q000008:administration & dosage / Q000494:pharmacology
D001552:Benzazepines; D017483:Receptors, Vasopressin; D014667:Vasopressins; C076251:mozavaptan; D005996:Nitroglycerin