Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy
Telmisartan, an angiotensin-II receptor blocker ameliorates cardiac remodeling in rats with dilated cardiomyopathy
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DOI：
10.1038/hr.2010.67
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Aizawa, Yoshifusa
中科院分区：
文献类型：
--
作者：
Sukumaran, Vijayakumar;Watanabe, Kenichi;Aizawa, Yoshifusa
过去几年的多项试验考察了血管紧张素受体阻滞剂(ARB)治疗左心室(LV)功能障碍的适应症，包括急性心肌梗死后和慢性心力衰竭(CHF)。然而，替米沙坦对实验性自身免疫性心肌炎(EAM)后慢性心力衰竭(CHF)大鼠的影响尚未被分析。用心肌肌球蛋白免疫Lewis大鼠诱发CHF，免疫28d后将存活的Lewis大鼠分为替米沙坦(10 mg·kg~(-1)·d~(-1))组和赋形剂组。治疗4周后，分析替米沙坦对EAM大鼠心功能、促炎细胞因子和心脏重塑的影响。与赋形剂治疗组相比，替米沙坦治疗充血性心力衰竭大鼠的血流动力学和超声心动图测定的心肌功能参数显著改善。替米沙坦显著降低模型组大鼠心肌纤维化、肥厚及其标志物(转化生长因子β1、I型和III型胶原、心钠素的LV mRNA表达)水平，以及过氧化体增殖物激活受体-c蛋白的表达。替米沙坦可抑制CHF诱导的心肌细胞炎性细胞因子(IL-6、IL-1β)、单核细胞趋化蛋白-1和基质金属蛋白酶(MMP2和-9)的表达。此外，替米沙坦治疗的大鼠血浆血管紧张素-II水平显著升高。我们的结果表明，替米沙坦治疗显著改善了EAM后CHF大鼠的左心功能，并改善了心脏重构的进展。高血压研究(2010年)33695702；DOI：10.1038/hr.2010.67；2010年6月10日在线发布
Multiple trials over the past several years have examined indications for angiotensin receptor blockers (ARBs) in the treatment of left ventricular (LV) dysfunction, both acutely after myocardial infarction and in chronic heart failure (CHF). However, the effects of telmisartan, an ARB in rats with CHF after experimental autoimmune myocarditis (EAM) have not yet been analyzed. CHF was elicited in Lewis rats by immunization with cardiac myosin, and 28 days after immunization, the surviving Lewis rats were divided into two groups and treated with either telmisartan (10 mg kg(-1) day(-1)) or vehicle. After 4 weeks of treatment, we analyzed the effects of telmisartan on cardiac function, proinflammatory cytokines and cardiac remodeling in EAM rats. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by telmisartan treatment in rats with CHF compared with those of vehicle-treated rats with CHF. Telmisartan significantly reduced levels of cardiac fibrosis, hypertrophy and its marker molecules ( LV mRNA expressions of transforming growth factor beta 1, collagen I and III, and atrial natriuretic peptide), and peroxisome proliferator-activated receptor-c protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1 beta), monocyte chemoattractant protein-1 and matrix metalloproteinases (MMP-2 and -9) were also suppressed by the treatment with telmisartan. Moreover, the plasma level of angiotensin-II was significantly elevated in telmisartan-treated rats. Our results indicate that telmisartan treatment significantly improved LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM. Hypertension Research (2010) 33, 695-702; doi: 10.1038/hr.2010.67; published online 10 June 2010