Faculty of Medicine, Department of Pharmacology, Assiut University, Assiut, Egypt 71526.
Fundam Clin Pharmacol. 2012 Dec;26(6):701-11. doi: 10.1111/j.1472-8206.2011.00975.x. Epub 2011 Sep 13.
In this study, the effects of simvastatin on the blood pressure and on the antihypertensive activity of ramipril in hypertensive hypercholesterolemic animals and patients were evaluated. In hypertensive hypercholesterolemic animals, repeated administration of simvastatin slightly but significantly decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of ramipril and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, ramipril or simvastatin in combination with ramipril to these animals, increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high sensitivity C-reactive protein (hs-CRP) levels. The effects of combined treatment were greater than those of simvastatin or ramipril alone. In hypertensive hypercholesterolemic patients, repeated administration of ramipril decreased systolic and diastolic blood pressure, increased NO production, and decreased the elevated serum MDA and hs-CRP levels. Addition of simvastatin to ramipril therapy enhanced these effects and corrected the compromised lipid profile. Simvastatin but not ramipril inhibited the contractile responses of isolated aortic rings induced by angiotensin 11. l-arginine and acetylcholine enhanced, while l-NAME inhibited effects of simvastatin, and simvastatin in combination with ramipril on these contractile responses. These findings suggest that simvastatin exerts antihypertensive effect and enhances the antihypertensive effect of ramipril in hypertensive hypercholesterolemic animals and patients. In addition to its cholesterol-lowering effect, the ability of simvastatin to ameliorate endothelial dysfunction through increasing NO bioavailability and through suppression of oxidative stress and vascular inflammation and its ability to enhance the effect of ramipril on these parameters may play a pivotal role in these effects.
在这项研究中，评估了辛伐他汀对高血压高脂血症动物和患者的血压和雷米普利的降压活性的影响。在高血压高脂血症动物中，辛伐他汀的重复给药略微但显著降低收缩压，增强了雷米普利重复给药引起的逐渐降低，并纠正了受损的脂质谱。同时，辛伐他汀、雷米普利或辛伐他汀与雷米普利联合重复给药增加了一氧化氮 (NO) 的产生，并降低了升高的血清丙二醛 (MDA) 和高敏 C 反应蛋白 (hs-CRP) 水平。联合治疗的效果大于辛伐他汀或雷米普利单独治疗的效果。在高血压高脂血症患者中，雷米普利的重复给药降低了收缩压和舒张压，增加了 NO 的产生，并降低了升高的血清 MDA 和 hs-CRP 水平。辛伐他汀与雷米普利治疗联合增强了这些作用并纠正了受损的脂质谱。辛伐他汀但不是雷米普利抑制了血管紧张素 11 诱导的离体主动脉环的收缩反应。l-精氨酸和乙酰胆碱增强了辛伐他汀的作用，而 l-NAME 抑制了辛伐他汀的作用以及辛伐他汀与雷米普利联合对这些收缩反应的作用。这些发现表明，辛伐他汀在高血压高脂血症动物和患者中发挥降压作用，并增强雷米普利的降压作用。除了降低胆固醇的作用外，辛伐他汀通过增加一氧化氮的生物利用度以及通过抑制氧化应激和血管炎症来改善内皮功能障碍的能力，以及增强雷米普利对这些参数的作用的能力，可能在这些作用中发挥关键作用。
