Darius H, Lefer A M
Proc Soc Exp Biol Med. 1985 Nov;180(2):364-8. doi: 10.3181/00379727-180-42190.
We studied the effects of thromboxane-receptor antagonism and thromboxane synthetase inhibition in a thrombotic model of sudden death in mice. Intravenous injection of arachidonic acid (AA; 80 mg/kg) or the prostaglandin-endoperoxide analog U-46,619 (2.3 mg/kg) results in sudden death in approximately 90% of the animals. Pretreatment with the thromboxane receptor antagonist SQ-29,548 (0.3-10 mg/kg) protects dose-dependently against AA and U-46,619-induced sudden death. In contrast, CGS-13,080, a thromboxane synthetase inhibitor, shows a dose-dependent beneficial effect in AA-induced sudden death only. Although PTA2 has partial thromboxane agonistic properties in the rabbit, it protected the mice against AA-induced sudden death, thus demonstrating TxA2 antagonistic properties in this species. These data emphasize the importance of thromboxane A2 as a major mediator of arachidonic acid-induced sudden death and the effectiveness of thromboxane-receptor antagonists in endoperoxide-induced sudden death.
我们在小鼠猝死的血栓形成模型中研究了血栓素受体拮抗作用和血栓素合成酶抑制作用的效果。静脉注射花生四烯酸（AA；80毫克/千克）或前列腺素内过氧化物类似物U - 46,619（2.3毫克/千克）会导致约90%的动物猝死。用血栓素受体拮抗剂SQ - 29,548（0.3 - 10毫克/千克）进行预处理可剂量依赖性地保护动物免受AA和U - 46,619诱导的猝死。相比之下，血栓素合成酶抑制剂CGS - 13,080仅在AA诱导的猝死中显示出剂量依赖性的有益效果。尽管PTA2在兔体内具有部分血栓素激动特性，但它能保护小鼠免受AA诱导的猝死，从而证明了该物种中存在血栓素A2拮抗特性。这些数据强调了血栓素A2作为花生四烯酸诱导猝死的主要介质的重要性，以及血栓素受体拮抗剂在过氧化物诱导猝死中的有效性。
