Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Hypertens Res. 2010 Jul;33(7):695-702. doi: 10.1038/hr.2010.67. Epub 2010 Jun 10.
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--gamma protein expression compared with those of vehicle-treated rats. CHF-induced increases in myocardial mRNA expressions of proinflammatory cytokines, (interleukin (IL)-6, IL-1beta), 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.
多项在过去几年进行的试验研究了血管紧张素受体阻断剂（ARB）在治疗左心室（LV）功能障碍方面的作用，包括心肌梗死后急性期和慢性心力衰竭（CHF）。然而，替米沙坦（ARB）在实验性自身免疫性心肌炎（EAM）后 CHF 大鼠中的作用尚未被分析。通过用心肌肌球蛋白免疫Lewis 大鼠诱发 CHF，免疫后 28 天，存活的 Lewis 大鼠被分为两组，分别用替米沙坦（10mg/kg/天）或载体处理。治疗 4 周后，我们分析了替米沙坦对 EAM 大鼠心脏功能、促炎细胞因子和心脏重构的影响。血流动力学和超声心动图研究测量的心肌功能参数显示，与 CHF 载体处理的大鼠相比，替米沙坦治疗显著改善了 CHF 大鼠的心脏功能。与 CHF 载体处理的大鼠相比，替米沙坦显著降低了心脏纤维化、肥大及其标志物分子（LV 转化生长因子β 1、I 型和 III 型胶原和心钠肽）的水平，以及过氧化物酶体增殖物激活受体-γ 蛋白表达。与 CHF 载体处理的大鼠相比，EAM 诱导的心肌促炎细胞因子（IL-6、IL-1β）、单核细胞趋化蛋白-1 和基质金属蛋白酶（MMP-2 和 MMP-9）的 mRNA 表达也被替米沙坦治疗所抑制。此外，替米沙坦治疗的大鼠血浆中血管紧张素 II 的水平显著升高。我们的结果表明，替米沙坦治疗显著改善了 EAM 后 CHF 大鼠的 LV 功能，并改善了心脏重构的进展。
