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Partial prevention of changes in SR gene expression in congestive heart failure due to myocardial infarction by enalapril or losartan

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Abstract

Although activation of the renin-angiotensin system (RAS) is known to produce ventricular remodeling and congestive heart failure (CHF), its role in inducing changes in the sarcoplasmic reticulum (SR) protein and gene expression in CHF is not fully understood. In this study, CHF was induced in rats by ligation of the left coronary artery for 3 weeks and then the animals were treated orally with or without an angiotensin converting enzyme inhibitor, enalapril (10 mg/kg/day) or an angiotensin II receptor antagonist, losartan (20 mg/kg/day) for 4 weeks. Sham-operated animals were used as control. The animals were hemodynamically assessed and protein content as well as gene expression of SR Ca2+-release channel (ryanodine receptor, RYR), Ca2+-pump ATPase (SERCA2), phospholamban (PLB) and calsequestrin (CQS) were determined in the left ventricle (LV). The infarcted animals showed cardiac hypertrophy, lung congestion, depression in LV +dP/dt and −dP/dt, as well as increase in LV end diastolic pressure. Both protein content and mRNA levels for RYR, SERCA2 and PLB were decreased without any changes in CQS in the failing heart. These alterations in LV function as well as SR protein and gene expression in CHF were partially prevented by treatment with enalapril or losartan. The results suggest that partial improvement in LV function by enalapril and losartan treatments may be due to partial prevention of changes in SR protein and gene expression in CHF and that these effects may be due to blockade of the RAS.

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  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre and Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Xiaobing Guo, Donald Chapman & Naranjan S. Dhalla

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  1. Xiaobing Guo
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Guo, X., Chapman, D. & Dhalla, N.S. Partial prevention of changes in SR gene expression in congestive heart failure due to myocardial infarction by enalapril or losartan. Mol Cell Biochem 254, 163–172 (2003). https://doi.org/10.1023/A:1027321130997

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