Eplerenone inhibits atherosclerosis in nonhuman primates
Eplerenone inhibits atherosclerosis in nonhuman primates
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DOI：
10.1161/01.hyp.0000184640.81730.22
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发表时间：
2005-11-01
期刊：
影响因子：
8.3
通讯作者：
Miyazaki, M
中科院分区：
文献类型：
--
作者：
Takai, S;Jin, D;Miyazaki, M
醛固酮可能参与了动脉粥样硬化的发病过程。我们研究了依普利酮（一种选择性盐皮质激素受体阻断剂）对高胆固醇饮食的猴子动脉粥样硬化的影响。将喂食高胆固醇饮食9个月的猴子分为3组：低剂量依普利酮（每天30 mg/kg）治疗组;高剂量依普利酮（每天60 mg/kg）治疗组;安慰剂治疗组。正常组由正常饮食的猴子组成。安慰剂和依普利酮治疗组之间的血压和胆固醇水平没有显著差异。另一方面，单核细胞趋化蛋白-1和丙二醛修饰的LDL在安慰剂治疗组中显著高于正常组，而在依普利酮治疗组中受到抑制。依普利酮治疗组的血管内超声分析成像的内膜体积与总体积的比值低于安慰剂治疗组，且呈剂量依赖性。安慰剂治疗组乙酰胆碱诱导的血管舒张作用明显弱于正常组，但依普利酮治疗组的血管舒张作用增强。在安慰剂治疗组中观察到血管紧张素转换酶活性的显著上调，但依普利酮治疗组的活性受到抑制。总之，依普利酮可以加强血管内皮依赖性舒张和抑制血管紧张素转换酶的活性，从而防止非人灵长类动物动脉粥样硬化的发展。
Aldosterone may be involved in the pathogenesis of atherosclerosis. We investigated the effect of eplerenone, a selective mineralocorticoid receptor blocker, on atherosclerosis in monkeys fed a high-cholesterol diet. Monkeys fed a high-cholesterol diet for 9 months were divided into 3 groups: those treated with a low dose of eplerenone (30 mg/kg per day); those treated with a high dose of eplerenone (60 mg/kg per day); and the placebo-treated group. The normal group consisted of monkeys fed a normal diet. There were no significant differences in blood pressure and cholesterol levels between the placebo- and eplerenone-treated groups. On the other hand, monocyte chemoattractant protein-1 and malondialdehyde-modified LDL were significantly higher in the placebo-treated group than in the normal group, whereas they were suppressed in the eplerenone-treated groups. The ratio of intimal volume to total volume by intravascular ultrasound analysis imaging of the aortas was dose-dependently lower in the eplerenone-treated groups than in the placebo-treated group. Acetylcholine-induced vasorelaxation was significantly weaker in the placebo-treated group than in the normal group, but the vasorelaxation was strengthened in the eplerenone-treated groups. A significant upregulation of angiotensin-converting enzyme activity was observed in the placebo-treated group, but the activity was suppressed in the eplerenone-treated groups. In conclusion, eplerenone may strengthen the endothelium-dependent relaxation and suppress angiotensin-converting enzyme activity in the vasculature, thus preventing the development of atherosclerosis in nonhuman primates.