Protective effects of ONO 3708, a new thromboxane A2 receptor antagonist, during experimental endotoxin shock.
The effects of ONO 3708, a new thromboxane A2 (TXA2) receptor antagonist, on platelet aggregation in human plasma, the survival rate of rats subjected to lethal endotoxin shock, and the pathophysiological consequences of endotoxin shock in anesthetized dogs were investigated. ONO 3708 inhibited dose dependently human platelet aggregation induced by 2.5 microM of STA2, analogue of TXA2. Treatment with ONO 3708, 1 mg/100 g i.v., significantly improved the survival rate of rats in endotoxin shock from 38 to 72% at 24 hr and from 27 to 61% at 48 hr. ONO 3708 significantly attenuated endotoxin-induced thrombocytopenia, but not leukopenia. In anesthetized dogs, endotoxin-induced pulmonary hypertension was completely prevented, and increased airway pressure was significantly attenuated by ONO 3708. These results suggest that ONO 3708, the antagonist of TXA2 receptor, has beneficial effects during endotoxin shock, at least in part by inhibiting platelet aggregation.