Sakata K, Shirotani M, Yoshida H, Urano T, Takada Y, Takada A
Department of Cardiology, Shizuoka General Hospital, Shizuoka, Japan.
Am Heart J. 1999 Jun;137(6):1094-9. doi: 10.1016/s0002-8703(99)70368-6.
Impaired fibrinolysis is associated with thromboembolic complications in hypertensive patients. It has been reported that cardiovascular morbidity and mortality rates are high even after lowering the elevated blood pressure with antihypertensive drugs. The aim of this study was to assess the effect of clinically used dosages of enalapril and nitrendipine on the fibrinolytic system.
Tissue plasminogen activator antigen (tPA) and tissue plasminogen activator inhibitor-1 (PAI-1) activity were measured in 20 normotensive male subjects and 46 male patients with mild essential hypertension divided into 2 groups (22 patients treated with 5 to 10 mg enalapril once a day and 24 treated with 5 to 10 mg nitrendipine once a day) before and 3 months after drug administration. Plasma renin activity and norepinephrine concentration were also measured.
There were no significant differences in basal characteristics between the 2 hypertensive groups. In both hypertensive groups, blood pressure was significantly reduced to a similar level after drug treatment. In the 2 hypertensive groups, plasma renin activity significantly increased after drug treatment; however, there were no significant changes in norepinephrine concentration. Before drug treatment, the 2 hypertensive groups had significantly higher tPA and higher PAI-1 activity than the normotensive subjects. In the enalapril group, there was no significant change in tPA although PAI-1 activity significantly decreased after drug treatment. In the nitrendipine group, there was no significant change in tPA although PAI-1 activity significantly increased after drug treatment.
Thus enalapril improved impaired fibrinolysis but nitrendipine further aggravated fibrinolysis in essential hypertension. Considering the effect of antihypertensive drugs on the fibrinolytic system, more effective and beneficial treatment of hypertensives, especially at a high risk for thrombus formation might be selected.
纤维蛋白溶解功能受损与高血压患者的血栓栓塞并发症相关。据报道，即使使用抗高血压药物降低了升高的血压，心血管疾病的发病率和死亡率仍然很高。本研究的目的是评估临床使用剂量的依那普利和尼群地平对纤维蛋白溶解系统的影响。
在20名血压正常的男性受试者和46名轻度原发性高血压男性患者中，测量给药前和给药3个月后组织纤溶酶原激活物抗原（tPA）和组织纤溶酶原激活物抑制剂-1（PAI-1）活性，这些患者被分为2组（22名患者每天服用5至10毫克依那普利，24名患者每天服用5至10毫克尼群地平）。还测量了血浆肾素活性和去甲肾上腺素浓度。
两个高血压组的基础特征没有显著差异。在两个高血压组中，药物治疗后血压均显著降低至相似水平。在两个高血压组中，药物治疗后血浆肾素活性显著增加；然而，去甲肾上腺素浓度没有显著变化。在药物治疗前，两个高血压组的tPA和PAI-1活性均显著高于血压正常的受试者。在依那普利组中，tPA没有显著变化，尽管药物治疗后PAI-1活性显著降低。在尼群地平组中，tPA没有显著变化，尽管药物治疗后PAI-1活性显著增加。
因此，依那普利改善了原发性高血压中受损的纤维蛋白溶解功能，但尼群地平进一步加重了纤维蛋白溶解功能。考虑到抗高血压药物对纤维蛋白溶解系统的影响，对于高血压患者，尤其是血栓形成风险高的患者，可能会选择更有效和有益的治疗方法。
