Sulotroban selectively inhibits thromboxane-receptor-mediated responses in the peripheral vascular bed of the cat

The effects of Sulotroban (BM 13.177, SK and F 95587) were investigated under conditions of controlled blood flow in the hindquarters and mesenteric vascular beds of the cat. Injections of the thromboxane (TX) A₂ mimics, U46619 and U44069, caused dose-related increases in perfusion pressure. After administration of SK and F 95587, vasoconstrictor responses to the TXA₂ mimics were reduced significantly, and the dose-response curves were shifted to the right in a parallel fashion. Responses to norepinephrine, phenylephrine, tyramine, endothelin-1, angiotensin II, BAY K8644, acetylcholine, sodium nitroprusside, isoproterenol, lemakalim, prostaglandin (PG) E₁, and PGF(2α), agents which alter vascular resistance by a variety of mechanisms, were not changed by the TXA₂ receptor antagonist. However, SK and F 95587 reduced mesenteric vasoconstrictor responses to PGD₂. Results of the present study indicate that SK and F 95587 blocks TX-receptor-mediated responses in the hindquarters circulation of the cat in a competitive and selective manner and reduces mesenteric vascular responses to the TXA₂ mimics, as well as PGD₂. These data suggest that this antagonist would be useful in studies on the role of TXA₂ in physiologic and pathophysiologic processes in the systemic vascular bed of the cat.