Department of Pharmacology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Fundam Clin Pharmacol. 2014 Jun;28(3):237-48. doi: 10.1111/fcp.12020. Epub 2013 Mar 13.
This study investigated whether simvastatin has antihypertensive activity and can enhance the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Hypertension and hypercholesterolemia were induced in rats by L-NAME and cholesterol-enriched diet, respectively. In these animals, repeated administration of simvastatin decreased the systolic blood pressure, enhanced its progressive reductions induced by repeated administration of losartan, and corrected the compromised lipid profile. Concomitantly, repeated administration of simvastatin, losartan, or simvastatin in combination with losartan to these animals increased nitric oxide (NO) production and decreased the elevated serum malondialdehyde (MDA) and high-sensitivity C-reactive protein (hs-CRP) levels. Effects of combined treatment were greater than those of simvastatin or losartan alone. In hypertensive hypercholesterolemic patients, repeated administration of losartan decreased systolic and diastolic blood pressure, increased NO production, and decreased the elevated serum MDA and hs-CRP levels. Addition of simvastatin to losartan therapy enhanced these effects and corrected the compromised lipid profile. Simvastatin inhibited the contractile responses of isolated aortic rings induced by angiotensin II and enhanced the inhibitory effect of losartan on this preparation. l-arginine and acetylcholine enhanced, while L-NAME inhibited the effects of simvastatin, losartan, and their combination on these contractile responses. Thus, simvastatin exerts antihypertensive effect in hypertensive hypercholesterolemic animals and enhances the antihypertensive effect of losartan in hypertensive hypercholesterolemic animals and patients. Besides, 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 may play an important role in these effects.
本研究旨在探讨辛伐他汀是否具有降压作用，并能增强高血压高脂血症动物和患者中氯沙坦的降压作用。通过 L-NAME 和富含胆固醇的饮食分别诱导大鼠高血压和高胆固醇血症。在这些动物中，辛伐他汀的重复给药降低了收缩压，增强了氯沙坦重复给药引起的逐渐降低，并纠正了受损的血脂谱。同时，辛伐他汀、氯沙坦或辛伐他汀联合氯沙坦重复给予这些动物可增加一氧化氮（NO）的产生，并降低升高的血清丙二醛（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氯沙坦单独治疗的效果。在高血压高脂血症患者中，氯沙坦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。辛伐他汀与氯沙坦联合治疗增强了这些作用，并纠正了受损的血脂谱。辛伐他汀抑制了血管紧张素 II 诱导的离体主动脉环的收缩反应，并增强了氯沙坦对该制剂的抑制作用。l-精氨酸和乙酰胆碱增强了辛伐他汀、氯沙坦及其联合应用对这些收缩反应的作用，而 L-NAME 则抑制了这些作用。因此，辛伐他汀在高血压高脂血症动物中具有降压作用，并增强了高血压高脂血症动物和患者中氯沙坦的降压作用。此外，辛伐他汀通过增加一氧化氮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，可能在这些作用中发挥重要作用。
