*Pharmacology division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India; †Academy of Scientific and Innovative Research, New Delhi, India; and ‡Clinical and Experimental Medicine division, Council of Scientific and Industrial Research-Central Drug Research Institute, Lucknow, India.
J Cardiovasc Pharmacol. 2017 Sep;70(3):176-183. doi: 10.1097/FJC.0000000000000503.
The accelerated generation of endothelial microparticles (EMPs) and impaired angiogenesis are the markers of vascular pathology during various cardiovascular and inflammatory conditions including hypertension. Because studies comparing the effects of antihypertensive agents on these 2 parameters are limited, this study was designed to compare the effects of 3 antihypertensive agents: aliskiren, nebivolol, and olmesartan, on the EMP generation and angiogenesis. Changes in the hemodynamic parameters and serum EMP count were determined after 3 weeks of the drug treatments [aliskiren (30 mg/kg), nebivolol (10 mg/kg), or olmesartan (5 mg/kg) per orally] in L-NAME-induced rat model of hypertension. The 3 drugs prevented the rise in blood pressure and EMP count to a similar extent. Furthermore, nebivolol was found to possess more potent and concentration-dependent antiangiogenic activity compared with aliskiren, whereas olmesartan was devoid of such an effect. The EMPs generated by virtue of the respective drug treatments were found to be involved in mediating the antiangiogenic effect of nebivolol and aliskiren. In addition, olmesartan treatment also resulted in the increased eNOS expression. The results of this study show that the antihypertensive drugs, viz. aliskiren, nebivolol, and olmesartan, regulate the vascular health by their differential effects on the EMP generation and angiogenesis.
内皮细胞微颗粒(EMP)的加速生成和血管生成受损是各种心血管和炎症状态下血管病理学的标志物,包括高血压。由于比较抗高血压药物对这两个参数影响的研究有限,因此本研究旨在比较三种抗高血压药物:阿利克仑、比索洛尔和奥美沙坦对 EMP 生成和血管生成的影响。在 L-NAME 诱导的高血压大鼠模型中,通过 3 周的药物治疗[阿利克仑(30mg/kg)、比索洛尔(10mg/kg)或奥美沙坦(5mg/kg)口服],确定血流动力学参数和血清 EMP 计数的变化。这 3 种药物均能在相似程度上预防血压升高和 EMP 计数的升高。此外,与阿利克仑相比,比索洛尔具有更强和浓度依赖性的抗血管生成活性,而奥美沙坦则没有这种作用。发现由于各自的药物治疗而产生的 EMP 参与介导了比索洛尔和阿利克仑的抗血管生成作用。此外,奥美沙坦治疗还导致 eNOS 表达增加。本研究结果表明,抗高血压药物,即阿利克仑、比索洛尔和奥美沙坦,通过对 EMP 生成和血管生成的不同作用来调节血管健康。