Veeraveedu Punniyakoti T, Watanabe Kenichi, Ma Meilei, Palaniyandi Suresh S, Yamaguchi Ken'ichi, Suzuki Kenji, Kodama Makoto, Aizawa Yoshifusa
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
Eur J Pharmacol. 2008 Feb 26;581(1-2):121-31. doi: 10.1016/j.ejphar.2007.11.034. Epub 2007 Nov 28.
Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular dysfunction. However, nothing is known about the effect of torasemide on myocardial remodeling in a rat model in which myosin-induced experimental autoimmune myocarditis might develop into dilated cardiomyopathy. Experimental autoimmune myocarditis was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, we investigated the effects of torasemide on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in experimental autoimmune myocarditis rats. Diuresis was increased dose-dependently by torasemide; the urinary potassium and sodium excretion was significantly decreased and increased, respectively. Myocardial functional parameters measured by hemodynamic and echocardiographic studies were significantly improved by torasemide treatment in a dose-dependent manner. The area of fibrosis, myocyte size and the myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase were significantly decreased, and the sarcoplasmic reticulum Ca2+ ATPase2 protein level was significantly increased by torasemide treatment. Moreover, the plasma levels of angiotensin II and aldosterone were increased and atrial natriuretic peptide was decreased in a dose-dependent manner. Our results indicate that torasemide treatment significantly improved left ventricular function and ameliorated the progression of cardiac remodeling beyond its renal effects in rats with chronic heart failure after experimental autoimmune myocarditis.
托拉塞米是一种长效袢利尿剂，兼具呋塞米和螺内酯的作用。据报道，托拉塞米可能会阻断肾素 - 血管紧张素 - 醛固酮系统，因此可能减轻伴有左心室功能障碍的心肌重塑。然而，在肌球蛋白诱导的实验性自身免疫性心肌炎可能发展为扩张型心肌病的大鼠模型中，关于托拉塞米对心肌重塑的影响尚无相关研究。通过用猪心肌肌球蛋白免疫Lewis大鼠诱发实验性自身免疫性心肌炎。免疫后28天，我们研究了托拉塞米对实验性自身免疫性心肌炎大鼠代谢和神经体液参数、心脏纤维化及重塑的影响。托拉塞米可使利尿呈剂量依赖性增加；尿钾排泄显著减少，尿钠排泄显著增加。通过血流动力学和超声心动图研究测量的心肌功能参数经托拉塞米治疗后呈剂量依赖性显著改善。托拉塞米治疗可使纤维化面积、心肌细胞大小以及转化生长因子 -β1、Ⅲ型胶原和醛固酮合酶的心肌蛋白水平显著降低，肌浆网Ca2+ ATP酶2蛋白水平显著升高。此外，血浆血管紧张素Ⅱ和醛固酮水平呈剂量依赖性升高，心房利钠肽水平呈剂量依赖性降低。我们的结果表明，在实验性自身免疫性心肌炎后发生慢性心力衰竭的大鼠中，托拉塞米治疗显著改善了左心室功能，并改善了心脏重塑的进程，其作用超出了其肾脏效应。
