Influence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarction

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dc.contributor.authorRen, B
dc.contributor.authorShao, QM
dc.contributor.authorGanguly, PK
dc.contributor.authorTappia, PS
dc.contributor.authorTakeda, N
dc.contributor.authorDhalla, NS
dc.date.accessioned2007-10-05T15:33:07Z
dc.date.available2007-10-05T15:33:07Z
dc.date.issued2004-12-31
dc.description.abstractAlthough 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 -70degreesC 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.en
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dc.identifier.citation0008-4212; CAN J PHYSIOL PHARMACOL, DEC 2004, vol. 82, no. 12, p.1118 to 1127.en
dc.identifier.doihttp://dx.doi.org/10.1139/y04-115
dc.identifier.urihttp://hdl.handle.net/1993/2892
dc.language.isoengen_US
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dc.rightsopen accessen_US
dc.statusPeer revieweden
dc.subjectsarcolemmal Na+/K+ ATPaseen
dc.subjectNa+-Ca2+ exchangeen
dc.subjectsarcoplasmic reticulumen
dc.subjectheart failureen
dc.subjectACE inhibitionen
dc.subjectCONVERTING ENZYME-INHIBITIONen
dc.subjectVENTRICULAR EJECTION FRACTIONSen
dc.subjectNA+-CA2+ EXCHANGERen
dc.subjectCALCIUM-TRANSPORTen
dc.subjectPROTEIN-LEVELSen
dc.subjectENALAPRILen
dc.subjectRATSen
dc.subjectCAPTOPRILen
dc.subjectHYPERTROPHYen
dc.subjectDYSFUNCTIONen
dc.titleInfluence of long-term treatment of imidapril on mortality, cardiac function, and gene expression in congestive heart failure due to myocardial infarctionen
dc.typejournal articleen_US
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