Although it is generally accepted that the efficacy of
imidapril, an
angiotensin-converting enzyme inhibitor, in
congestive heart failure (CHF) is due to improvement of hemodynamic parameters, the significance of its effect on gene expression for sarcolemma (SL) and sarcoplasmic reticulum (SR)
proteins has not been fully understood. In this study, we examined the effects of long-term treatment of
imidapril on mortality, cardiac function, and gene expression for SL Na+/K+
ATPase and Na+ -Ca2+ exchanger as well as SR Ca2+ pump
ATPase, Ca2+ release channel (
ryanodine receptor),
phospholamban, and
calsequestrin in CHF due to
myocardial infarction.
Heart failure subsequent to
myocardial infarction was induced by occluding the left coronary artery in rats, and treatment with
imidapril (1 mg.kg(-1).day(-1)) was started orally at the end of 3 weeks after surgery and continued for 37 weeks. The animals were assessed hemodynamically and the heart and lung were examined morphologically. Some hearts were immediately frozen at -70 degrees C for the isolation of
RNA as well as SL and SR membranes. The mortality of
imidapril-treated animals due to
heart failure was 31% whereas that of the untreated
heart failure group was 64%.
Imidapril treatment improved cardiac performance, attenuated cardiac remodeling, and reduced morphological changes in the heart and lung. The depressed SL Na+/K+
ATPase and increased SL Na+-Ca2+ exchange activities as well as reduced SR Ca2+ pump and SR Ca2+ release activities in the failing hearts were partially prevented by
imidapril. Although changes in gene expression for SL Na+/K+
ATPase isoforms as well as Na+-Ca2+ exchanger and SR
phospholamban were attenuated by treatments with
imidapril, no alterations in
mRNA levels for SR Ca2+ pump
proteins and Ca2+ release channels were seen in the untreated or treated rats with
heart failure. These results suggest that the beneficial effects of
imidapril in CHF may be due to improvements in cardiac performance and changes in SL gene expression.