Triphasic response of rat intracerebral arterioles to increasing concentrations of vasopressin in vitro.
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% increased]. 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 endothelium-derived relaxing factor activated by vasopressin. Both vasodilation and vasoconstriction were found to be mediated through vasopressin V1 receptors in a study of arterioles pretreated with d(CH2)5Tyr(Me)arginine vasopressin (10(-6) M), a vasopressin V1 receptor antagonist. These results support the hypothesis that vasopressin may constrict smaller cerebral arterioles while simultaneously dilating larger cerebral arteries. Our results also suggest that vasopressin may aggravate cerebral ischemia in pathological conditions, such as subarachnoid hemorrhage, when the arteriolar response to vasopressin shifts from vasodilation to vasoconstriction due to increased vasopressin levels in plasma and CSF and impaired endothelium-derived relaxation.
Takayasu
M
M
Department of Neurosurgery, School of Medicine, Nagoya University, Japan.
Kajita
Y
Y
Suzuki
Y
Y
Shibuya
M
M
Sugita
K
K
Ishikawa
T
T
Hidaka
H
H
D000818:Animals; D001160:Arterioles / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017483:Receptors, Vasopressin / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology*
D017483:Receptors, Vasopressin; D014667:Vasopressins; D009569:Nitric Oxide