Bourgain R H, Andries R, Decuyper K, De Clerck F
Laboratory of Physiology and Physiopathology, Faculty of Medicine, V.U.B., Belgium.
J Lipid Mediat. 1991 Jan-Feb;3(1):3-11.
In rats treated with acetylsalicylic acid (100 mg/kg i.v., -3 h) to block platelet cyclo-oxygenase, a superfusion with tranylcypromine (TCP, 3 x 10(-3) M) plus arachidonic acid (AA; 1 x 10(-4) M) significantly enhances (+70%) the opto-electronically monitored formation of a thrombus, elicited by a superfusion with ADP (4 x 10(-4) M for 45 s) over a de-endothelialized site of a mesenteric artery (200-300 microns diameter). Treatment with ridogrel at doses blocking either singly thromboxane A2 (TxA2) synthetase (0.63 mg/kg i.v., -15 min, n = 6) or additionally TxA2/prostaglandin endoperoxide receptors (5 mg/kg i.v., -15 min, n = 6) reduces (-74%) or abolishes (-100%) respectively the enhancement by TCP + AA of the ADP-induced thrombus formation. These observations demonstrate (1) a transfer of prostaglandin endoperoxides from the vessel wall to the platelets to reinforce thrombus formation in vivo; (2) the antithrombotic potential of combined TxA2 synthetase inhibition plus TxA2/prostaglandin endoperoxide receptor blockade with ridogrel.
在用乙酰水杨酸（100毫克/千克静脉注射，-3小时）处理以阻断血小板环氧化酶的大鼠中，用反苯环丙胺（TCP，3×10⁻³M）加花生四烯酸（AA；1×10⁻⁴M）进行超灌注，可显著增强（+70%）由在直径为200 - 300微米的肠系膜动脉去内皮部位用ADP（4×10⁻⁴M，持续45秒）进行超灌注引发的血栓的光电监测形成。用利度卡因单剂量阻断血栓素A2（TxA2）合成酶（0.63毫克/千克静脉注射，-15分钟，n = 6）或额外阻断TxA2/前列腺素内过氧化物受体（5毫克/千克静脉注射，-15分钟，n = 6）进行治疗，分别降低（-74%）或消除（-100%）了TCP + AA对ADP诱导的血栓形成的增强作用。这些观察结果表明：（1）前列腺素内过氧化物从血管壁转移到血小板以在体内增强血栓形成；（2）利度卡因联合抑制TxA2合成酶加阻断TxA2/前列腺素内过氧化物受体具有抗血栓形成潜力。
