Captopril treatment improves the sarcoplasmic reticular Ca2+ transport in heart failure due to myocardial infarction

Although captopril. an angiotensin-converting enzyme (ACE) inhibitor, has b een shown to exert a beneficial effect on cardiac function in heart failure , its effect on the status of sarcoplasmic reticulum (SR) Ca2+ transport in the failing heart has not been examined previously. In order to determine whether captopril has a protective action on cardiac function, as well as c ardiac SR Ca2+-pump activity and gene expression. a rat model of heart Fail ure due to mycardial infarction was employed in this study. Sham operated a nd infarcted rats were given captopril (2 g/l) in drinking water, this trea tment was started at either 3 or 21 days and was carried out until 8 weeks after the surgery. The untreated animals with myocardial infarction showed increased heart weight and elevated left ventricular end diastolic pressure , reduced rates of pressure development and pressure fall, as well as depre ssed SR Ca2+ uptake and Ca2+-stimulated ATPase activities in comparison wit h the sham control group. These hemodynamic and biochemical changes in the failing hearts were prevented by treatment of the infarcted animals with ca ptopril. Likewise, the observed reductions in the SR Ca2+ pump and phosphol amban protein contents. as well as in the mRNA levels for SR Ca2+ pump ATPa se and phospholamban, in the failing heart were attenuated by captopril tre atment, These results suggest that heart failure is associated with a defec t in the SR Ca2+ handling and a depression in the gene expression of SR pro teins: the beneficial effect of captopril in heart failure may be due to it sm ability to prevent remodeling of the cardiac SR membrane. (C) 1999 Acade mic Press.