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.
Ohkusa
T
T
Second Department of Internal Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Hisamatsu
Y
Y
Ueyama
T
T
Kobayashi
S
S
Yano
M
M
Maekawa
T
T
Matsuzaki
M
M
D000818:Animals; D001012:Aorta, Abdominal; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D003620:Dantrolene / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D006352:Heart Ventricles / Q000187:drug effects; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009125:Muscle Relaxants, Central / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014661:Vasoconstriction
D009125:Muscle Relaxants, Central; D003620:Dantrolene; D002118:Calcium