Seuter F, Perzborn E, Fiedler V B
Institute of Pharmacology, Bayer AG, Wuppertal, FRG.
Stroke. 1990 Dec;21(12 Suppl):IV146-8.
Bay U 3405 [(3R)-3-(4-fluorophenylsulfonamido)-1,2,3,4-tetrahydro-9- carbazolepropanoic acid] potently inhibits platelet aggregation, thromboxane A2-induced contraction of smooth muscles, and coronary artery thrombosis. We have previously demonstrated inhibition of arachidonic acid-induced sudden death by Bay U 3405. The purpose of this study was to investigate the effects of Bay U 3405 on thromboembolism provoked by collagen. Collagen fibrils dissolved in an isotonic glucose solution were injected into a marginal ear vein of anesthetized rabbits. Sudden death occurred within a few minutes due to elevated thromboxane A2 levels causing intravascular platelet aggregation and myocardial ischemia. In the vehicle-treated group, 100% of the animals died. One of the most prominent parameters was the massive fall in blood pressure. All animals pretreated with 10 mg/kg orally Bay U 3405 survived, showing only a transient hypotensive effect. Tracings of the electrocardiogram and heart rate were unchanged. Bay U 3405 will therefore be useful to elucidate the role of thromboxane A2 in various cardiovascular and respiratory diseases.
Bay U 3405 [即(3R)-3-(4-氟苯基磺酰胺基)-1,2,3,4-四氢咔唑丙酸] 能有效抑制血小板聚集、血栓素A2诱导的平滑肌收缩以及冠状动脉血栓形成。我们之前已经证明Bay U 3405可抑制花生四烯酸诱导的猝死。本研究的目的是探讨Bay U 3405对胶原蛋白诱发的血栓栓塞的影响。将溶解于等渗葡萄糖溶液中的胶原纤维注射到麻醉兔的耳缘静脉。由于血栓素A2水平升高导致血管内血小板聚集和心肌缺血，几分钟内就会发生猝死。在赋形剂处理组中，100%的动物死亡。最显著的参数之一是血压大幅下降。所有口服10 mg/kg Bay U 3405预处理的动物均存活，仅表现出短暂的降压作用。心电图和心率描记图未发生变化。因此，Bay U 3405将有助于阐明血栓素A2在各种心血管和呼吸系统疾病中的作用。
