The Novel Thromboxane A₂ Receptor Antagonist KW-3635 Abolishes the Cyclic Flow Reduction in the Canine Carotid Artery

Abstract

We tested the hypothesis that the abolition of the cyclic flow reduction (CFR) in the canine carotid artery is related to inhibition of ex vivo platelet aggregation following administration of KW-3635, a thromoxane A₂ receptor antagonist, or aspirin. The CFR was induced in the carotid artery of anesthetized dogs by mechanical injury and narrowing of the artery. After induction of CFR, KW-3635 or aspirin was administered every 30 min at doses of 0, 1, 0.3, 1 and 3 mg/kg (i.v.). The ex vivo platelet aggregation, induced by sodium arachidonate and collagen, was also examined before and 15 min after each administration. KW-3635 and aspirin, at doses of 1 mg/kg i.v. and above, inhibited CFR and ex vivo platelet aggregation. These results suggest that CFR in the canine carotid artery is platelet-dependent.