Shah, KGanguly, PNetticadan, TArneja, ADhalla, N2007-10-052007-10-052004-07-31Canadian Journal of Physiology and Pharmacology, JUL 2004;. 82(7):438-447.http://hdl.handle.net/1993/2896In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca2+-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca2+-uptake and Ca2+-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca2+-uptake and Ca2+-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca2+-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca2+-pump for Ca2+. Furthermore, the stimulation of SR Ca2+-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT(1)R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca2+-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca2+-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca2+-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca2+-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.113036 bytesapplication/pdfengskeletal musclesarcoplasmic reticulumCa2+-transportSR Ca2+-pumpcongestive heart failurerenin-angiotensin systemSARCOPLASMIC-RETICULUMGENE-EXPRESSIONDIABETIC CARDIOMYOPATHYEXERCISE INTOLERANCECALCIUM-TRANSPORTBLOOD-FLOWRATSABNORMALITIESRELEASEFATIGUEjournal article10.1139/Y04-051