Buczko Włodzimierz, Kubik Andrzej, Kucharewicz Iwona, Chabielska Ewa
Department of Pharmacodynamics, Medical University of Białystok, Mickiewicza 2c, PL 15-089 Białystok, Poland.
Pol J Pharmacol. 2004 Jan-Feb;56(1):97-104.
Angiotensin converting enzyme inhibitors (ACE-Is) are the main drugs used in the treatment of essential hypertension and congestive heart failure in adults. Recently, we have demonstrated the antithrombotic effect of captopril (CAP) and enalapril (ENA) in venous thrombosis model in adult rats. One might also suggest the beneficial effect of those drugs on hemostasis in young individuals. Two months old male Wistar rats were used in the study. Acute administration of CAP at a dose of 50 and 100 mg kg(-1) significantly reduced the venous thrombus weight. Dose-dependent reduction in the thrombus weight was also observed in ENA (3, 10, 30 mg kg(-1))-treated rats. Strong reduction in the thrombus weight was also seen after chronic administration of CAP (2 x 25 mg kg(-1)) and ENA (1 x 15 mg kg(-1)). Both drugs given chronically reduced the frequency of thrombi. Systolic blood pressure was reduced to similar extent after acute and chronic application of the drugs. CAP shortened euglobulin clot lysis time (ECLT) when given acutely (100 mg kg(-1)) and chronically (2 x 25 mg kg(-1)). ENA decreased ECLT only when given at multiple doses (1 x 15 mg kg(-1)). None of the drugs changed prothrombin time or activated partial tromboplastin time. We conclude that CAP and ENA possess antithrombotic effect in young individuals. Activation of the fibrinolytic pathway seems to play an important role in the mechanism of their antithrombotic action.
血管紧张素转换酶抑制剂（ACE-Is）是治疗成人原发性高血压和充血性心力衰竭的主要药物。最近，我们已经在成年大鼠静脉血栓形成模型中证实了卡托普利（CAP）和依那普利（ENA）的抗血栓作用。也有人可能会认为这些药物对年轻人的止血有有益作用。本研究使用了2个月大的雄性Wistar大鼠。急性给予剂量为50和100mg/kg（-1）的CAP可显著降低静脉血栓重量。在接受ENA（3、10、30mg/kg（-1））治疗的大鼠中也观察到血栓重量呈剂量依赖性降低。长期给予CAP（2×25mg/kg（-1））和ENA（1×15mg/kg（-1））后，血栓重量也显著降低。两种药物长期给药均降低了血栓形成的频率。急性和慢性应用这些药物后，收缩压降低到相似程度。急性（100mg/kg（-1））和慢性（2×25mg/kg（-1））给予CAP时可缩短优球蛋白凝块溶解时间（ECLT）。仅在多次给药（1×15mg/kg（-1））时，ENA才会降低ECLT。这些药物均未改变凝血酶原时间或活化部分凝血活酶时间。我们得出结论，CAP和ENA在年轻人中具有抗血栓作用。纤维蛋白溶解途径的激活似乎在其抗血栓作用机制中起重要作用。
