Pharmacological Effect of Endothelin, an Endothelium-derived Vasoconstrictive Peptide, on Canine Basilar Arteries

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The purpose of this study was to evaluate the constrictive effect of endothelin, a peptide vasoconstrictor derived from endothelium, on canine basilar artery. Constriction was measured by an isometric tension recording method. Endothelin induced prolonged contraction of canine basilar aftery in a dose-dependent fashion, the estimated concentration at 50% contraction being (2.1±0.5)×10^<-9> M (mean±SEM). Removal of endothelium significantly augmented the arterial response to endothelin. In Ca^<++>-free medium no contractile response was elicited at 10^<-8> M endothelin. Papaverine (10^<-4> M) and nicardipine (10^<-8> M), a calcium channel blocker, almost completely inhibited the contraction induced by 10^<-8> M endothelin. Pretreatment with nicardipine (10^<-8>-10^<-6> M) also significantly suppressed the response to endothelin. Acetylcholine (10^<-7>-10^<-4> M), adenosine triphosphate (10^<-7>-10^<-5> M), and thrombin (0.1 and 1.0 U/ml) dose-dependently inhibited contraction of canine basilar artery in response to 3×10^<-9> M endothelin. These results show that endothelin has a potent constrictive effect on canine basilar artery and suggest that this substance may play an important role in the pathogenesis of vasospasm following subarachnoid hemorrhage.
日本脳神経外科学会の論文
1989-11-15