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This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/H1674    most recent 00945.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Shao, Q. Articles by Dhalla, N. S. Search for Related Content PubMed PubMed Citation Articles by Shao, Q. Articles by Dhalla, N. S.

Sarcoplasmic reticulum Ca²⁺ transport and gene expression in congestive heart failure are modified by imidapril treatment

¹Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada; and ²Department of Internal Medicine, Jikei University, Tokyo, Japan

Submitted 10 September 2004 ; accepted in final form 10 November 2004

This study was designed to test the hypothesis that blockade of the renin-angiotensin system improves cardiac function in congestive heart failure by preventing changes in gene expression of sarcoplasmic reticulum (SR) proteins. We employed rats with myocardial infarction (MI) to examine effects of an angiotensin-converting enzyme inhibitor, imidapril, on SR Ca²⁺ transport, protein content, and gene expression. Imidapril (1 mg·kg^–1·day^–1) was given for 4 wk starting 3 wk after coronary artery occlusion. Infarcted rats exhibited a fourfold increase in left ventricular end-diastolic pressure, whereas rates of pressure development and decay were decreased by 60 and 55%, respectively. SR Ca²⁺ uptake and Ca²⁺ pump ATPase, as well as Ca²⁺ release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for Ca²⁺ pump ATPase, phospholamban, and ryanodine receptor were also decreased by 55–65%. Imidapril treatment of infarcted animals improved cardiac performance and attenuated alterations in SR Ca²⁺ pump and Ca²⁺ release activities. Changes in protein content and mRNA levels for SR Ca²⁺ pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR Ca²⁺ transport were not only seen at different intervals of MI but were also simulated by another angiotensin-converting enzyme inhibitor, enalapril, and an ANG II receptor antagonist, losartan. These results suggest that blockade of the renin-angiotensin system may increase the abundance of mRNA for SR proteins and, thus, may prevent the depression in SR Ca²⁺ transport and improve cardiac function in congestive heart failure due to MI.

myocardial infarction; cardiac gene expression; renin-angiotensin system

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