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首页> 外文期刊>Clinical and experimental pharmacology & physiology >Additive beneficial effects of amlodipine and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive rats.
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Additive beneficial effects of amlodipine and atorvastatin in reversing advanced cardiac hypertrophy in elderly spontaneously hypertensive rats.

机译：氨氯地平和阿托伐他汀在老年人自发性高血压大鼠逆转晚期心脏肥厚中的添加剂有益效果。

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1. Additive beneficial effects on cardiovascular disease have been reported for amlodipine and atorvastatin. However, it is still unclear whether the combination of amlodipine and atorvastatin has additive beneficial effects on the regression of advanced cardiac hypertrophy in hypertension. In the present study, the effects of the drug combination on advanced cardiac hypertrophy were investigated in elderly spontaneously hypertensive rats (SHR). 2. Elderly SHR (36 weeks old) were randomly allocated into four groups of 12: (i) a vehicle-treated control group; (ii) an amlodipine (10 mg/kg per day)-treated group; (iii) an atorvastatin (10 mg/kg per day)-treated group; and (iv) a group treated with a combination of amlodipine and atorvastatin (both at 10 mg/kg per day). Drugs were administered by oral gavage every morning for a period of 12 weeks before hearts were harvested for analysis. 3. Combined administration of amlodipine and atorvastatin significantly suppressed cardiomyocyte hypertrophy, interstitial fibrosis and upregulation of hypertrophic and profibrotic genes, and also improved left ventricular diastolic dysfunction to a greater extent than did amlodipine monotherapy. Further beneficial effects of combination therapy on advanced cardiac hypertrophy were associated with a greater reduction of NADPH oxidase-mediated increases in cardiac reactive oxygen species (ROS), rather than decreased blood pressure and serum cholesterol levels. 4. To elucidate the underlying molecular mechanisms, we examined cardiovascular NADPH oxidase subunits and found that amlodipine clearly attenuated the expression of p47(phox) and p40(phox) and slightly but significantly reduced p22(phox) and Rac-1 levels in heart tissue. Combination treatment with amlodipine plus atorvastatin led to a further reduction in p22(phox), p47(phox) and Rac-1 protein levels compared with amlodipine alone. 5. In conclusion, combined amlodipine and atorvastatin treatment has a greater beneficial effect on advanced cardiac hypertrophy compared with amlodipine monotherapy. The benefits are likely to be related to the additive effects of the drugs on the suppression of NADPH oxidase-mediated ROS generation.
机译：据报道，氨氯地平和阿托伐他汀报道了对心血管疾病的添加剂有益效果。然而，仍然目前还不清楚氨氯地平和阿托伐他汀的组合是否对高血压晚期心脏肥厚的回归具有添加剂有益的影响。在本研究中，在老年人自发性高血压大鼠（SHR）中研究了药物组合对晚期心脏肥大的影响。 2.年长SHR（36周龄）随机分配为四组12：（i）载体处理的对照组; （ii）氨氯普（每天10mg / kg） - 治疗组; （iii）阿托伐他汀（每天10mg / kg） - 治疗组; （iv）用氨氯地脂和阿托伐他汀（Atorvastatin组合（每天10mg / kg）治疗的组。每天早上每天早上饲喂药物12周，以在收获术前进行分析。 3.组合氨氯地平和阿托伐他汀的施用显着抑制了心肌细胞肥大，间质纤维化和衰弱性和俯冲基因的上调，并在更大程度上改善了左心室舒张功能障碍，而不是氨氯地平单疗法。联合治疗对晚期心脏肥大的进一步有益效果与NADPH氧化酶介导的心脏反应性氧物质（ROS）的增加较大相关，而不是降低血压和血清胆固醇水平。 4.为了阐明潜在的分子机制，我们检查了心血管NADPH氧化酶亚基，发现氨氯锥管明显减毒了P47（PHOX）和P40（PHOX）的表达，略微但显着减少了心脏组织中的RAC-1水平。 。与单独单独的氨氯普滨相比，用氨氯地平加阿托伐他汀的组合处理导致P22（PHOX），P47（PHOX）和RAC-1蛋白水平的进一步减少。 5.结论，与氨氯地平单药治疗相比，氨氯地平和阿托伐他汀治疗的组合对晚期心脏肥厚具有更大的有益效果。这些益处可能与药物对抑制NADPH氧化酶介导的ROS产生的效果有关。

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