EFFECTS OF DANTROLENE SODIUM ON PROGRESSION OF LEFT-VENTRICULAR HYPERTROPHY INDUCED BY PRESSURE-OVERLOAD IN RATS

We studied the long-term effects of dantrolene sodium (D), a specific sarcoplasmic reticulum (SR) Ca2+-release inhibitor, on the progression of left ventricular pressure-overloaded hypertrophy in rats. We treat ed abdominal aorta-constricted rats with one of two doses of D for 3 w eeks. The extent of hypertrophy was expressed as the ratio of left ven tricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in dr inking water) decreased blood pressure to normal levels, the progressi on of cardiac hypertrophy was not inhibited. In contrast, a high dose of D (5 mg/kg, i.p.) also reduced blood pressure and inhibited the pro gression of cardiac hypertrophy. Dantrolene sodium had no effect on ca rdiac function in sham-operated rats. Thus control of Ca2+ release fro m the SR might be crucial in regulating the progression of cardiac hyp ertrophy, the final mediator possibly being intracellular Ca2+ concent ration.