Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy

• Published in: European journal of pharmacology Vol. 581; no. 1; pp. 121 - 131
• Main Authors: Veeraveedu, Punniyakoti T., Watanabe, Kenichi, Ma, Meilei, Palaniyandi, Suresh S., Yamaguchi, Ken'ichi, Suzuki, Kenji, Kodama, Makoto, Aizawa, Yoshifusa
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 26-02-2008; Elsevier
• Subjects: Aldosterone; Animals; Atrial Natriuretic Factor - blood; Biological and medical sciences; Body Weight - drug effects; Cardiology. Vascular system; Cardiomyopathy, Dilated - prevention & control; Collagen Type III - analysis; Disease Progression; Diuretics - therapeutic use; Experimental autoimmune myocarditis; Fibrosis; Heart; Heart Failure - drug therapy; Male; Matrix Metalloproteinase 9 - genetics; Medical sciences; Myocarditis - drug therapy; Myocarditis. Cardiomyopathies; Myocardium - chemistry; Myocardium - pathology; Pharmacology. Drug treatments; Rats; Rats, Inbred Lew; Remodeling; RNA, Messenger - analysis; Sulfonamides - therapeutic use; Torasemide; Transforming Growth Factor beta1 - analysis; Ventricular Function, Left - drug effects; Experimental autoimmune myocarditis; Remodeling; Aldosterone; Torasemide; Fibrosis; Autoimmunity; Steroid hormone; Mineralocorticoid; Cardiovascular disease; Myocardial disease; Diuretic; Myocarditis; Dilated cardiomyopathy; Sulfonamides; Heart disease; Adrenal hormone
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2007.11.034

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 Ca
2+ 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.