Comparative effects of torasemide and furosemide in rats with heart failure.
It has been reported that torasemide but not furosemide, may block the renin-angiotensin-aldosterone system and therefore it might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. We therefore compared the therapeutic effects of torasemide, a long-acting loop diuretic, and furosemide, a short-acting one, on the progression of LV remodeling in a rat model of chronic heart failure (CHF) after experimental autoimmune myocarditis (EAM). CHF was elicited in Lewis rats by immunization with porcine cardiac myosin. Twenty-eight days after immunization, rats were treated for 28 days with torasemide, furosemide, or vehicle. We investigated the effects on metabolic and neurohumoral parameters, cardiac fibrosis and remodeling in EAM rats. Diuresis was increased dose dependently by both torasemide and furosemide, showed an equipotent natriuretic effect. The urinary potassium excretion was significantly increased with furosemide in comparison to torasemide. Myocardial functional parameters were significantly improved by torasemide. Conversely, these parameters did not change in rats receiving furosemide. Torasemide suppressed LV fibrosis, myocardial protein levels of transforming growth factor-beta1, collagen III, and aldosterone synthase and improved survival rate to the control level, but furosemide did not. Moreover, both pharmacological interventions significantly elevated plasma angiotensin II and decreased atrial natriuretic peptide in a dose-dependent manner. Our results demonstrate that compared with furosemide, torasemide treatment significantly improved survival rate, LV function and ameliorated the progression of cardiac remodeling in rats with CHF after EAM.
Veeraveedu
Punniyakoti T
PT
Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima Akiha-ku, Niigata City, Niigata, Japan.
Watanabe
Kenichi
K
Ma
Meilei
M
Thandavarayan
Rajarajan A
RA
Palaniyandi
Suresh S
SS
Yamaguchi
Ken'ichi
K
Suzuki
Kenji
K
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
D000818:Animals; D024061:Collagen Type III / Q000032:analysis; D019405:Cytochrome P-450 CYP11B2 / Q000032:analysis; D004232:Diuretics / Q000627:therapeutic use*; D005665:Furosemide / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009206:Myocardium / Q000737:chemistry / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D013449:Sulfonamides / Q000627:therapeutic use*; D015996:Survival Rate; D000077786:Torsemide; D053773:Transforming Growth Factor beta1 / Q000032:analysis; D016277:Ventricular Function, Left / Q000187:drug effects
D024061:Collagen Type III; D004232:Diuretics; D013449:Sulfonamides; D053773:Transforming Growth Factor beta1; D005665:Furosemide; D019405:Cytochrome P-450 CYP11B2; D000077786:Torsemide