Pharmacological Reversal of Subcellular Remodeling in Heart Failure due to Myocardial Infarction

In order to test if cardiac dysfunction and defects in subcellular organelles such as sarcoplasmic reticulum (SR), myofibrils (MF) and sarcolemma (SL) in heart failure are reversible, we treated the 12 weeks infarcted rats with or without prazosin (alpha-adrenoceptor blocker), metoprolol (beta-adrenoceptor blocker) or losartan (angiotensin II receptor blocker) for 8 weeks. Cardiac dysfunction, as reflected by depressed +dP/dt and -dP/dt, as well as decreased SR Ca2+-uptake and SL Na+-K+ ATPase activities in 20 weeks infarcted animals were partially reversed by prazosin, metoprolol or losartan treatment. On the other hand, depressed SR Ca2+-release and MF Ca2+-stimulated ATPase activities in the failing hearts were not affected by prazosin, metoprolol or losartan treatment. These results suggest that partial improvement in cardiac dysfunction in heart failure due to myocardial infarction is associated with partial attenuation of SR and SL remodeling by treatment with prazosin, metaprolol and losartan.