Takayasu M, Kajita Y, Suzuki Y, Shibuya M, Sugita K, Ishikawa T, Hidaka H
Department of Neurosurgery, School of Medicine, Nagoya University, Japan.
J Cereb Blood Flow Metab. 1993 Mar;13(2):304-9. doi: 10.1038/jcbfm.1993.38.
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.
为了确定血管加压素如何影响较小脑动脉的血管张力，我们对大鼠分离并插管的脑内小动脉进行了一项体外研究。我们发现，血管加压素浓度增加会诱导三相反应，即血管舒张（10⁻¹² - 10⁻¹¹ M）、血管收缩（10⁻¹⁰ - 10⁻⁸ M）以及血管舒张并稳定至对照直径（10⁻⁷ - 10⁻⁶ M），并且在这些较小的动脉中，最大收缩幅度是最大舒张幅度的两倍[直径减少21.2±13.1%（平均值±标准差），而直径增加11.2±5.7%]。用内皮源性舒张因子的特异性抑制剂NG - 单甲基 - L - 精氨酸（10⁻⁴ M）对小动脉进行预处理，消除了血管加压素诱导的血管舒张，并显著增加了血管收缩。这些结果表明，这些小动脉通过血管加压素激活的内皮源性舒张因子维持在舒张状态。在一项用血管加压素V1受体拮抗剂d(CH₂)₅Tyr(Me)精氨酸血管加压素（10⁻⁶ M）预处理小动脉的研究中发现，血管舒张和血管收缩均通过血管加压素V1受体介导。这些结果支持这样一种假说，即血管加压素可能会使较小的脑动脉收缩，同时使较大的脑动脉扩张。我们的结果还表明，在病理状况下，如蛛网膜下腔出血，当血浆和脑脊液中血管加压素水平升高以及内皮源性舒张受损导致小动脉对血管加压素的反应从血管舒张转变为血管收缩时，血管加压素可能会加重脑缺血。
