Tagawa T, Imaizumi T, Shiramoto M, Endo T, Hironaga K, Takeshita A
Research Institute of Angiocardiology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Cardiovasc Pharmacol. 1995 Mar;25(3):387-92. doi: 10.1097/00005344-199503000-00006.
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.
精氨酸加压素（AVP）可引起人前臂血管阻力的双相变化：低剂量时血管收缩，高剂量时血管舒张。血管收缩由V1受体介导，但AVP诱导血管舒张的机制尚不清楚。为了确定人前臂血管中AVP诱导的血管舒张是否由V2受体介导，我们研究了OPC - 31260（一种新型加压素V2受体拮抗剂）对AVP诱导的血管舒张的影响。将肱动脉插管用于药物输注和直接测量动脉血压（BP）。我们用应变片体积描记器测量前臂血流量（FBF），并计算前臂血管阻力（FVR）。以0.1、0.2、0.5、1.0和2.0 ng/kg/min的剂量动脉内（i.a.）输注AVP（n = 8）。较低剂量的AVP（0.1 ng/kg/min）使FVR升高，而较高剂量的AVP（≥0.5 ng/kg/min）使FVR降低（p < 0.01）。静脉内（i.v.）输注剂量为1.7、3.3和10.0 ng/kg/min的硝酸甘油（NTG）可剂量依赖性地降低FVR（p < 0.01）。动脉内输注OPC - 31260（1.0微克/千克/分钟）不会改变动脉血压、基线FVR或心率（HR）。OPC - 31260不影响AVP诱导的血管收缩，但完全阻断AVP诱导的血管舒张。OPC - 31260不影响NTG诱导的血管舒张。这些结果表明，AVP诱导的血管舒张是由人前臂阻力血管中的V2受体介导的。
