Liao P, Johnson G, Siegfried M, Lefer A M
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Eicosanoids. 1989;2(1):33-7.
Sodium arachidonate (NaAr) at a dose of 1.1 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 marked rise in plasma thromboxane A2 (TxA2) concentration as measured by radioimmunoassay of its breakdown product, TxB2. Pretreatment with S-145, a new thromboxane receptor antagonist, at doses ranging from 50 to 500 micrograms/kg resulted in 100% survival of all the rabbits subjected to sodium arachidonate injection. However, at 20 micrograms/kg S-145 only 25% of the rabbits challenged with NaAr survived. S-145 pretreatment also inhibited the decreases in circulating platelet count and in blood pressure associated with the i.v. injection of sodium arachidonate (NaAr). S-145 blunted the rise in plasma TxB2 concentration at all doses. S-145 was also shown to be a potent and long-lasting antagonist of TxA2 receptors in isolated rabbit aortic rings. Our data show that S-145 is a very effective protective agent against NaAr-induced sudden death in rabbits.
静脉注射剂量为1.1毫克/千克的花生四烯酸钠（NaAr）在5分钟内会使兔子全部死亡。这种突然死亡的特征是平均动脉血压急剧下降、循环血小板计数显著减少，以及通过对其分解产物血栓素B2（TxB2）进行放射免疫测定发现血浆血栓素A2（TxA2）浓度显著升高。用新型血栓素受体拮抗剂S-145进行预处理，剂量范围为50至500微克/千克，可使所有接受花生四烯酸钠注射的兔子100%存活。然而，在20微克/千克的S-145剂量下，用NaAr攻击的兔子中只有25%存活。S-145预处理还抑制了与静脉注射花生四烯酸钠（NaAr）相关的循环血小板计数和血压的下降。S-145在所有剂量下都能抑制血浆TxB2浓度的升高。在离体兔主动脉环中，S-145还被证明是TxA2受体的强效和长效拮抗剂。我们的数据表明，S-145是一种非常有效的预防兔子因NaAr诱导的猝死的保护剂。
