Protective effects of a new specific thromboxane antagonist in arachidonate-induced sudden death.

Sodium arachidonate (NaAr), at a dose of 2.0 mg/kg injected i.v., is uniformly lethal in rabbits within 5 min. This sudden death is typified by a precipitous drop in mean arterial blood pressure, a dramatic decrease in the circulating platelet count, and by a sharp rise in plasma thromboxane A2 (TxA2) concentration. Pretreatment with BM-13,505, a novel thromboxane receptor antagonist, at doses ranging from 0.25 mg/kg to 2.0 mg/kg resulted in 100% survival of rabbits subjected to sodium arachidonate injection. BM-13,505 pretreatment also inhibited the decreases in circulating platelet count and in blood pressure associated with arachidonic acid injection. BM-13,505 did not inhibit the sharp rise in plasma TxB2 concentrations at any dose. This evidence suggests that the mechanism of BM-13,505 protection is by means of thromboxane receptor antagonism and not via inhibition of thromboxane A2 synthesis.