Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade
Date
2004-07-31
Authors
Shah, K
Ganguly, P
Netticadan, T
Arneja, A
Dhalla, N
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Abstract
In 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.
Description
Keywords
skeletal muscle, sarcoplasmic reticulum, Ca2+-transport, SR Ca2+-pump, congestive heart failure, renin-angiotensin system, SARCOPLASMIC-RETICULUM, GENE-EXPRESSION, DIABETIC CARDIOMYOPATHY, EXERCISE INTOLERANCE, CALCIUM-TRANSPORT, BLOOD-FLOW, RATS, ABNORMALITIES, RELEASE, FATIGUE
Citation
Canadian Journal of Physiology and Pharmacology, JUL 2004;. 82(7):438-447.