Wahed Mir Imam Ibne, Watanabe Kenichi, Ma Meilei, Yamaguchi Kenichi, Takahashi Toshihiro, Tachikawa Hitoshi, Kodama Makoto, Aizawa Yushifusa
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata-shi, Japan.
Pharmacology. 2005 Feb;73(2):81-8. doi: 10.1159/000081267. Epub 2004 Oct 1.
Aldosterone blockade reduces morbidity and mortality in patients with heart failure. We studied the effects of eplerenone, a novel aldosterone blocker, on the progression of left ventricular dysfunction and remodeling in rats with dilated cardiomyopathy after autoimmune myocarditis. Twenty-eight days after immunization, the surviving Lewis rats were randomized to 1 month's oral treatment with low-dose eplerenone (group L), high-dose eplerenone (group H) or vehicle (group V). Five of 15 (33%) rats in group V and 3 of 15 (20%) rats in group L died during the course of treatment. High-dose eplerenone significantly reduced cardiomyocyte hypertrophy, heart weight and heart weight to body weight ratio. Eplerenone improved left ventricular function in a dose-dependent manner. Central venous pressure and left ventricular end-diastolic pressure were lower, and +/-dP/dt and fractional shortening were higher in group H than group V. Eplerenone also attenuated myocardial fibrosis and reduced left ventricular mRNA expressions of TGF-beta(1) and collagen-III. Our results indicate that treatment with eplerenone improved left ventricular dysfunction and attenuated left ventricular remodeling in rats with heart failure.
醛固酮拮抗剂可降低心力衰竭患者的发病率和死亡率。我们研究了新型醛固酮拮抗剂依普利酮对自身免疫性心肌炎后扩张型心肌病大鼠左心室功能障碍进展和重塑的影响。免疫后28天，将存活的Lewis大鼠随机分为三组，分别接受为期1个月的低剂量依普利酮口服治疗（L组）、高剂量依普利酮口服治疗（H组）或赋形剂治疗（V组）。治疗过程中，V组15只大鼠中有5只（33%）死亡，L组15只大鼠中有3只（20%）死亡。高剂量依普利酮显著减轻心肌细胞肥大、心脏重量及心脏重量与体重之比。依普利酮以剂量依赖方式改善左心室功能。H组中心静脉压和左心室舒张末期压力较低，+/-dP/dt和缩短分数高于V组。依普利酮还可减轻心肌纤维化，并降低左心室TGF-β(1)和胶原蛋白III的mRNA表达。我们的结果表明，依普利酮治疗可改善心力衰竭大鼠的左心室功能障碍并减轻左心室重塑。
