Pharmacological effect of endothelin, an endothelium-derived vasoconstrictive peptide, on canine basilar arteries

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 artery in a dose-dependent fashion, the estimated concentration at 50% contraction being (2.1 +/- 0.5) X 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 X 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.