Attenuation of changes in sarcoplasmic reticular gene expression in cardiac hypertrophy by propranolol and verapamil

The effects of propranolol and verapamil on contractile dysfunction, subcel lular remodeling and changes in gene expression in cardiac hypertrophy due to pressure overload were examined. Rats were subjected to banding of the a bdominal aorta and then treated with either propranolol (10 mg/kg daily), v erapamil (5 mg/kg daily) or vehicle for 8 weeks after the surgery. Depressi on of the left ventricular function in the hypertrophied heart was associat ed with decreases in myofibrillar and myosin CA(2+) ATPase activities as we ll as Ca2+-pump and Ca2+-release activities of the sarcoplasmic reticulum ( SR). The level of alpha -myosin heavy chain (alpha -MHC) mRNA was decreased while that of beta -MHC mRNA was increased in the pressure-overloaded hear t. The level of SR Ca2+-pump ATPase (SERCA2) mRNA and protein content for S ERCA2 were decreased in the pressure overloaded heart. Treatment of the hyp ertrophied animals with propranolol or verapamil resulted in preservation o f the left ventricular function and prevention of the subcellular alteratio ns. Shift in the alpha- and beta -MHC mRNA levels and changes in the expres sion in SERCA2 mRNA level and protein content were also attenuated by these treatments. The results suggest that blockade of beta -adrenoceptors or vo ltage-dependent calcium channels normalizes the cardiac gene expression, pr events subcellular remodeling and thus attenuates heart dysfunction in rats with cardiac hypertrophy. Furthermore, both cardiac beta -adrenoceptors an d L-type Ca2+-channels may be involved in the genesis of cardiac hypertroph y due to pressure overload.