Triphasic response of rat intracerebral arterioles to increasing concentrations of vasopressin in vitro

Abstract

To determine how vasopressin affects the vascular tone of the smaller cerebral arterioles, we carried out an in vitro study of isolated and cannulated intracerebral arterioles of rats. We found that increasing concentrations of vasopressin induced a triphasic response of vasodilation (10-12-10-11 M), vasoconstriction (10-10-10-8 M), and vasodilation stabilizing to control diameter (10-7-10-6 M) and that the maximum constriction was twice the maximum dilation in these smaller arterioles [21.2 ± 13.1% (mean ± SD) decrease in diameter vs. 11.2 ± 5.7% increase]. Pretreatment of the arterioles with NG-monomethyl-L-arginine (10-4 M), a specific inhibitor of endothelium-derived relaxing factor, abolished the vasopressin-induced vasodilation and significantly increased the vasoconstriction. These results suggest that these arterioles were maintained in a dilated state by an endothe-lium-derived relaxing factor activated by vasopre Both vasodilation and vasoconstriction were fouad a mediated through vasopressin VI receptors in a stut arterioles pretreated with d(CH2)5Tyr(Me)arginine pressin (10-6 M), a vasopressin V1 receptor antaglog These results support the hypothesis that vasop may constrict smaller cerebral arterioles while sin neously dilating larger cerebral arteries. Our results suggest that vasopressin may aggravate cerebral isch in pathological conditions, such as subarachnoid his rhage, when the arteriolar response to vasopressin she from vasodilation to vasoconstriction due to increased vasopressin levels in plasma and CSF and impaired on dothelium-derived relaxation.