title: Torasemide, a long-acting loop diuretic, reduces the progression of myocarditis to dilated cardiomyopathy.
abstract: 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.
authors.affiliation: Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata City, Japan.
authors.forename: Punniyakoti T
authors.initials: PT
authors.lastname: Veeraveedu
authors.forename: Kenichi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Meilei
authors.initials: M
authors.lastname: Ma
authors.forename: Suresh S
authors.initials: SS
authors.lastname: Palaniyandi
authors.forename: Ken'ichi
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Suzuki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000517:prevention & control*; D024061:Collagen Type III / Q000032:analysis; D018450:Disease Progression; D004232:Diuretics / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009205:Myocarditis / Q000188:drug therapy*; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011917:Rats, Inbred Lew; D013449:Sulfonamides / Q000627:therapeutic use*; D000077786:Torsemide; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D024061:Collagen Type III; D004232:Diuretics; D012333:RNA, Messenger; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; D009320:Atrial Natriuretic Factor; D020780:Matrix Metalloproteinase 9; D000077786:Torsemide