Sarcoplasmic reticulum [Ca.sup.2+] transport and gene expression in congestive heart failure are modified by imidapril treatment

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 [Ca.sup.2+] transport, protein content, and gene expression. Imidapril (1 mg x [kg.sup.-1] x [day.sup.-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 [Ca.sup.2+] uptake and [Ca.sup.2+] pump ATPase, as well as [Ca.sup.2+] release and ryanodine receptor binding activities, were depressed in the failing hearts; protein content and mRNA levels for [Ca.sup.2+] 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 [Ca.sup.2+] pump and [Ca.sup.2+] release activities. Changes in protein content and mRNA levels for SR [Ca.sup.2+] pump ATPase, phospholamban, and ryanodine receptor were also prevented by imidapril treatment. Beneficial effects of imidapril on cardiac function and SR [Ca.sup.2+] 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 [Ca.sup.2+] transport and improve cardiac function in congestive heart failure due to MI. myocardial infarction; cardiac gene expression; renin-angiotensin system