A NOVEL ENDOTHELIN ET(A) RECEPTOR ANTAGONIST, BQ-485, AND ITS PREVENTIVE EFFECT ON EXPERIMENTAL CEREBRAL VASOSPASM IN DOGS

Because endothelin-1 has a potent and long-lasting vasoconstrictive action, it has been proposed that it plays some important roles in the pathogenesis of delayed cerebral vasospasm following subarachnoid hemorrhage. We examined the preventive effect of a novel ETA receptor antagonist, BQ-485, on experimental vasospasm using canine two-hemorrhage model of subarachnoid hemorrhage. The IC50 value of BQ-485 on [125I]endothelin-1 binding was 3.4×10-9 M for ETA receptor and 26×10-6 M for ETB receptor. Systemic continuous administration of 120 mg/day of the agent inhibited the narrowing of canine basilar artery on day 7 following experimental subarachnoid hemorrhage (75.0% vs 59.9% (control), p<0.01). The present results suggest that endothelin-1 and ETA receptor participate in the pathogenesis of delayed cerebral vasospasm. © 1993 Academic Press, Inc.