Tanaka Hiroko, Watanabe Kenichi, Harima Meilei, Thanikachalam Punniyakoti Veeraveedu, Yamaguchi Ken'ichi, Tachikawa Hitoshi, Kodama Makoto, Aizawa Yoshifusa
Department of Clinical Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan.
Yakugaku Zasshi. 2009 Jul;129(7):871-9. doi: 10.1248/yakushi.129.871.
Torasemide is a long-acting loop diuretic that combines the effects of both furosemide and spironolactone. It has been reported that torasemide but not furosemide might attenuate myocardial remodeling accompanied by left ventricular (LV) dysfunction. However, nothing is known about the effect of torasemide, long-acting loop diuretic and spironolactone, an aldosterone receptor antagonist in a rat model of chronic heart failure (CHF). Therefore, we compared the therapeutic effects of torasemide, furosemide and spironolactone on the progression of LV remodeling in a rat model of CHF after experimental autoimmune myocarditis (EAM). EAM 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 and spironolactone. Diuretic actions, heart weight/body weight, heart rate, mean blood pressure, myocardial function by echocardiography, cardiac fibrosis, myocyte diameter and cardiac aldosterone synthetase (CYP11B2) were evaluated. Increased cardiac CYP11B2, severe LV remodeling and resultant cardiac dysfunction was found in CHF rats, whereas decreased cardiac CYP11B2, less remodeling and improvement of cardiac function were found in torasemide- and spironolactone-treated CHF rats. Our results indicate that torasemide and spironolactone treatment significantly improved cardiac function and LV remodeling compared with furosemide treatment.
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,托拉塞米而非呋塞米可能会减轻伴有左心室(LV)功能障碍的心肌重塑。然而,在慢性心力衰竭(CHF)大鼠模型中,对于托拉塞米这种长效袢利尿剂和醛固酮受体拮抗剂螺内酯的作用尚无了解。因此,我们比较了托拉塞米、呋塞米和螺内酯对实验性自身免疫性心肌炎(EAM)后CHF大鼠模型中LV重塑进展的治疗效果。通过用猪心肌肌凝蛋白免疫Lewis大鼠诱发EAM。免疫后28天,用托拉塞米、呋塞米和螺内酯对大鼠进行28天的治疗。评估利尿作用、心脏重量/体重、心率、平均血压、超声心动图检测的心肌功能、心脏纤维化、心肌细胞直径和心脏醛固酮合成酶(CYP11B2)。在CHF大鼠中发现心脏CYP11B2增加、严重LV重塑及由此导致的心脏功能障碍,而在托拉塞米和螺内酯治疗的CHF大鼠中发现心脏CYP11B2降低、重塑减轻及心脏功能改善。我们的结果表明,与呋塞米治疗相比,托拉塞米和螺内酯治疗显著改善了心脏功能和LV重塑。