Inhibition of Endothelin-converting Enzyme Activity in the Rabbit Basilar Artery

Abstract

OBJECTIVE 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. METHODS 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 × 10−6 mol/L). RESULTS In the group pretreated with [d-Val22]big ET-1[16–38] (2 × 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 × 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). CONCLUSION 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.