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 treated abdominal aorta-constricted rats with one of two doses of D for 4 weeks. The extent of hypertrophy was expressed as the ratio of left ventricle to body weight. Hemodynamic parameters were measured by using a microtip catheter manometer. Although a low dose of D (500 mg/L in drinking water) decreased blood pressure to normal levels, the progression 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 progression of cardiac hypertrophy. Dantrolene sodium had no effect on cardiac function in sham-operated rats. Thus control of Ca2+ release from the SR might be crucial in regulating the progression of cardiac hypertrophy, the final mediator possibly being intracellular Ca2+ concentration.