Ekholm Mikael, Jekell Andreas, Wallén N Håkan, Gigante Bruna, Kahan Thomas
Division of Cardiovascular Medicine, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden.
Unit of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
J Cardiovasc Pharmacol. 2018 Apr;71(4):240-247. doi: 10.1097/FJC.0000000000000565.
Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We examined the contribution of the angiotensin-converting enzyme inhibitor ramipril and the alpha 1-adrenergic receptor blocker doxazosin on blood pressure and on markers of inflammation and hemostasis in 59 individuals with mild-to-moderate hypertension randomized to receive double-blind ramipril 10 mg od or doxazosin 8 mg od for 12 weeks. Inflammatory markers (interleukin-6, soluble interleukin-6 receptor, interleukin-8, tumor necrosis factor-α, monocyte chemoattractant protein-1, and C-reactive protein) and hemostasis (plasminogen activator inhibitor-1 activity, tissue plasminogen activator antigen, thrombin-antithrombin complex, and thrombin generation by calibrated automated thrombogram) were assessed. The treatment reduced blood pressure in both groups. Thrombin-antithrombin complex decreased by treatment, and this was dependent on a reduction in thrombin-antithrombin complex in the ramipril group alone. There were no changes in plasminogen activator inhibitor-1 activity, whereas tissue plasminogen activator antigen increased by ramipril and decreased by doxazosin. Only minor changes were observed in systemic inflammation by treatment. Treatment with ramipril seems to reduce thrombin generation beyond effects on reducing blood pressure. Drugs blocking the renin-angiotensin-aldosterone system may reduce atherothrombotic complications beyond their effects to reduce blood pressure.
除了具有降低血压的作用外，阻断肾素-血管紧张素-醛固酮系统的药物可能在内皮功能、炎症及止血方面带来益处。我们对59例轻至中度高血压患者进行了研究，这些患者被随机分为两组，分别接受双盲治疗，一组每天口服10毫克雷米普利，另一组每天口服8毫克多沙唑嗪，为期12周，我们观察了血管紧张素转换酶抑制剂雷米普利和α1-肾上腺素能受体阻滞剂多沙唑嗪对血压以及炎症和止血标志物的影响。评估了炎症标志物（白细胞介素-6、可溶性白细胞介素-6受体、白细胞介素-8、肿瘤坏死因子-α、单核细胞趋化蛋白-1和C反应蛋白）和止血指标（纤溶酶原激活物抑制剂-1活性、组织纤溶酶原激活物抗原、凝血酶-抗凝血酶复合物以及通过校准自动血栓图检测的凝血酶生成情况）。两组治疗均降低了血压。治疗后凝血酶-抗凝血酶复合物减少，且这仅取决于雷米普利组凝血酶-抗凝血酶复合物的降低。纤溶酶原激活物抑制剂-1活性无变化，而雷米普利使组织纤溶酶原激活物抗原增加，多沙唑嗪使其减少。治疗对全身炎症仅产生轻微变化。雷米普利治疗似乎在降低血压之外还能减少凝血酶生成。阻断肾素-血管紧张素-醛固酮系统的药物可能在降低血压之外还能减少动脉粥样硬化血栓形成并发症。
