The in vivo antiaggregatory action of endothelin-1 is not mediated through the endothelin ETA receptor.

Intravenous bolus injection of endothelin-1 (0.1 and 0.25 nmol/kg) resulted in a dose-dependent inhibition of in vivo platelet aggregation in anesthetized Beagle dogs. Pretreatment of the animals with the selective ETA receptor antagonist, BQ-123 (1 mg/kg), completely abolished the pressor response to endothelin-1 without affecting the magnitude of the depressor response. BQ-123 neither modified the antiaggregatory action of endothelin-1 nor affected the increase in plasma 6-keto prostaglandin F1 alpha level elicited by endothelin-1. These findings indicate that the in vivo antiaggregatory and prostacyclin releasing actions of endothelin-1 are not mediated by activation of the ETA receptor.