Inhibition of endothelin-converting enzyme activity in the rabbit basilar artery.

Abstract

Endothelin (ET)-1 may be involved in the regulation of cerebrovascular resistance under pathological conditions, most notably during the development of vasospasm after subarachnoid hemorrhage. Blocking ET-converting enzyme activity may be a promising approach to the prevention of cerebral vasospasm after subarachnoid hemorrhage. In this study, the effects of several putative ET-converting enzyme inhibitors were investigated after intracisternal application in rabbits, to inhibit basilar artery contractions induced by big ET-1 (2 x 10(-6) mol/L). In the group pretreated with [D-Val22]big ET-1[16-38] (2 x 10(-5) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.63 +/- 0.12 mm to 0.66 +/- 0.12 mm. In the control group (n = 8), the diameter of the basilar artery decreased from 0.71 +/- 0.13 mm to 0.57 +/- 0.15 mm. These results corresponded to an increase in vessel diameter of 5 +/- 10% in the treatment group and a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014). In the group pretreated with captopril (2 x 10(-4) mol/L) (n = 8), the angiographically measured diameter of the basilar artery changed from 0.64 +/- 0.11 mm to 0.71 +/- 0.10 mm. These results corresponded to an increase in vessel diameter of 14 +/- 19% in the treatment group, compared with a decrease in vessel diameter of 20 +/- 16% in the control group (P = 0.014). These results demonstrate that [D-Val22]big ET-1[16-38] and captopril act as highly potent ET-converting enzyme inhibitors, affecting big ET-1-induced contraction of the rabbit basilar artery.