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1 & Dept. of Physiology, Faculty of Medicine, University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface Gen. Hosp. Research Centre, Winnipeg, MB, Canada
2 & Human Nutritional Sciences, Faculty of Human Ecology, University of Manitoba, Institute of Cardiovascular Sciences, St. Boniface Gen. Hosp. Research Centre, Winnipeg, MB, Canada
3 Department of Internal Medicine, Jikei University, Aoto Hospital, Tokyo, Japan
* To whom correspondence should be addressed. E-mail: nsdhalla{at}sbrc.ca.
The activities of both sarcolemmal (SL) Na+-K+ ATPase and Na+-Ca2+ exchanger, which maintain the intracellular cation homeostasis, have been shown to be depressed in heart failure due to myocardial infarction (MI). Since the renin-angiotensin system (RAS) is activated in heart failure, this study tested the hypothesis that attenuation of cardiac SL changes in congestive heart failure (CHF) by angiotensin converting enzyme (ACE) inhibitors is associated with prevention of alterations in gene expression for SL Na+-K+ ATPase and Na+-Ca2+ exchanger. CHF in rats due to MI was induced by occluding the coronary artery and 3 weeks later the animals were treated with an ACE inhibitor, imidapril (1 mg/kg/day), for 4 weeks. Heart dysfunction and cardiac hypertrophy in the infarcted animals were associated with depressed SL Na+-K+ ATPase and Na+-Ca2+ exchange activities. Protein content and mRNA levels for Na+-Ca2+ exchanger as well as Na+-K+ ATPase 
1-, 2- and 
1-isoforms were depressed whereas those for 3-isoform were increased in the failing heart. These changes in SL activities, protein content and gene expression were attenuated by treating the infarcted animals with imidapril. The beneficial effects of imidapril treatment on heart function, cardiac hypertrophy as well as SL Na+-K+ ATPase and Na+-Ca2+ exchange activities in the infarcted animals were simulated by enalapril, an ACE inhibitor, and losartan, an angiotensin receptor antagonist. These results suggest that blockade of RAS in CHF improves SL Na+-K+ ATPase and Na+-Ca2+ exchange activities in the failing heart by preventing changes in gene expression for SL proteins.
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