Pawlak R, Chabielska E, Golatowski J, Azzadin A, Buczko W
Department of Pharmacodynamics, Medical School, Białystok, Poland.
Thromb Haemost. 1998 Jun;79(6):1208-12.
The long-term administration of captopril to patients with a left ventricular dysfunction after myocardial infarction reduces the rate of recurrent coronary thrombosis. Thus, in the present study we investigated the influence of angiotensin-converting enzyme inhibitors (ACE-Is) on experimental venous thrombosis in normotensive rats and the involvement of NO and PGI2 in this effect. Animals were treated with captopril (1.5, 5 or 25 mg/kg twice daily, CAP), enalapril (15 mg/kg once daily, ENA) or distilled water for 10 days, per os. After ligation of the vena cava the thrombus weight decreased in both CAP and ENA treated rats. The effect was most pronounced in animals given the highest dose of CAP (p<0.0001 vs. control) and was significantly stronger than observed in ENA treated animals (CAP vs. ENA p<0.01). The mean blood pressure measured by the "tail cuff" method and platelet aggregation were not altered by either of the ACE-Is. The antithrombotic activity of CAP was reduced by indomethacin (2.5 mg/kg, s.c.) and independently by the NO-synthase inhibitor N(G)-nitro L-arginine methyl ester (3 mg/kg i.v. bolus + 3 mg/kg/h i.v. infusion, L-NAME). In the latter case CAP regained its antithrombotic properties in rats pretreated with L-Arginine (300 mg/kg i.v. + 300 mg/kg/h i.v.) before administration of L-NAME (p<0.05 vs. control). Moreover, the concomitant administration of indomethacin and L-NAME failed to completely abolish the antithrombotic action of captopril. Similar effects were observed in respect to the incidence of venous thrombosis. Our study documents a novel and important effect of ACE-Is on the vein thrombotic process and demonstrates the involvement of NO and PGI2 in this phenomenon.
对心肌梗死后左心室功能不全患者长期给予卡托普利可降低冠状动脉血栓复发率。因此，在本研究中，我们调查了血管紧张素转换酶抑制剂（ACE-Is）对正常血压大鼠实验性静脉血栓形成的影响以及一氧化氮（NO）和前列环素（PGI2）在此效应中的作用。动物经口给予卡托普利（1.5、5或25mg/kg，每日两次，CAP）、依那普利（15mg/kg，每日一次，ENA）或蒸馏水，持续10天。腔静脉结扎后，CAP和ENA处理的大鼠血栓重量均降低。在给予最高剂量CAP的动物中，这种效应最为明显（与对照组相比，p<0.0001），且明显强于ENA处理的动物（CAP与ENA相比，p<0.01）。通过“尾套”法测量的平均血压和血小板聚集均未因任何一种ACE-Is而改变。吲哚美辛（2.5mg/kg，皮下注射）可降低CAP的抗血栓活性，而一氧化氮合酶抑制剂N(G)-硝基-L-精氨酸甲酯（3mg/kg静脉推注+3mg/kg/h静脉输注，L-NAME）也可独立降低其活性。在后一种情况下，在给予L-NAME之前用L-精氨酸（300mg/kg静脉注射+300mg/kg/h静脉注射）预处理的大鼠中，CAP恢复了其抗血栓特性（与对照组相比，p<0.05）。此外，吲哚美辛和L-NAME联合给药未能完全消除卡托普利的抗血栓作用。在静脉血栓形成的发生率方面也观察到了类似的效果。我们的研究记录了ACE-Is对静脉血栓形成过程的一种新的重要作用，并证明了NO和PGI2参与了这一现象。
