Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade

• Published in: Canadian journal of physiology and pharmacology 2004-07, Vol.82 (7), p.438-447
• Main Authors: Shah, Kanu R, Ganguly, Pallab K, Netticadan, Thomas, Arneja, Amarjit S, Dhalla, Naranjan S
• Format: Article
• Language: English
• Subjects: Angiotensin II - antagonists & inhibitors; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Apoptosis; Biological and medical sciences; Calcium - metabolism; Calcium-Transporting ATPases - metabolism; Captopril - pharmacology; Cyclic AMP-Dependent Protein Kinases - metabolism; Enalapril - pharmacology; Fundamental and applied biological sciences. Psychology; Heart Failure - enzymology; Heart Failure - etiology; Heart Failure - physiopathology; Imidazolidines - pharmacology; Losartan - pharmacology; Male; Muscle, Skeletal - metabolism; Muscular Atrophy - etiology; Myocardial Infarction - complications; Rats; Rats, Sprague-Dawley; Sarcoplasmic Reticulum - enzymology; Time Factors; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0008-4212; 1205-7541
• DOI: 10.1139/y04-051

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) Ca 2+ -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 Ca 2+ -uptake and Ca 2+ -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 Ca 2+ -uptake and Ca 2+ -stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca 2+ -transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca 2+ -pump for Ca 2+ . Furthermore, the stimulation of SR Ca 2+ -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 Ca 2+ -pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca 2+ -transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca 2+ -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 Ca 2+ -transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.Key words: skeletal muscle, sarcoplasmic reticulum, Ca 2+ -transport, SR Ca 2+ -pump, congestive heart failure, renin-angiotensin system.