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Please use this identifier to cite or link to this item: http://hdl.handle.net/1993/913

Title: Membrane remodeling in heart failure due to myocardial infarction in rats
Authors: Shao, Qiming
Issue Date: 1-May-1997
Abstract: By employing a rat model of heart failure following coronary occlusion, we have tested the hypothesis that beneficial effects of imidapril (IMP), a long acting angiotensin converting enzyme inhibitor, on heart failure are associated with revention of Ca$\sp{2+}$-handling abnormalities in cardiomyocytes. In this study, IMP (1 mg/kg, daily) was given orally for 4 weeks starting 3 weeks after coronary occlusion (myocardial infarction) or sham operation. Untreated sham control or infarcted rats were given saline under similar conditions. Occlusion of the coronary artery in rats for 7 weeks was found to result in cardiac hypertrophy, elevation in left ventricular end diastolic pressure (LVEDP) and depression in both rates of contraction (+dP/dt) and relaxation ($-$dP/dt) without any changes in the heart rate or left ventricular systolic pressure. Treatment of infarcted animals with IMP prevented these changes in heart function fully or partially without significantly affecting the scar weight or the increase inleft ventricular weight. The depression in ATP-induced increases in left ventricular developed pressure, +dP/dt and $-$dP/dt in the infarcted animals was also prevented by IMP treatment. In view of the crucial role played by sarcolemma (SL) in the control of Ca$\sp{2+}$-movements in cardiomyocytes, we examined the status of SL remodeling in the failing hearts subsequent to myocardial infarction. The SL Na$\sp{+}$-K$\sp{+}$ ATPase activity was depressed in the failing left ventricles and this was accompanied by a decrease in the $\alpha\sb1$-, $\alpha\sb2$-, and $\beta\sb1$-isoform and an increase in $\alpha\sb3$-isoform contents in the SL membrane. A depression in mRNA levels for $\alpha\sb1$-, $\alpha\sb2$-, and $\beta\sb1$-isoforms and an increase in $\alpha\sb3$-isoform of Na$\sp{+}$-K$\sp{+}$ ATPase were also observed in the failing hearts. These changes in Na$\sp{+}$-K$\sp{+}$ ATPase isoforms were partially or fully prevented by treatment of infarcted animals with IMP. The depression in Na$\sp{+}$-dependent Ca$\sp{2+}$-uptake activity and protein content as well as mRNA levels for a$\sp{+}$-Ca$\sp{+}$ exchange in the failing hearts was also fully or partially prevented by IMP treatment. We investigated the status of Ca$\sp{2+}$-pump and Ca$\sp{2+}$-release channels in sarcoplasmic reticulum (SR) membranes from the failing left ventricles subsequent to myocardial infarction. The activities of ATP-dependent Ca$\sp{2+}$-uptake and Ca$\sp{2+}$-stimulated ATPase as well as protein contents of Ca$\sp{2+}$-pump ATPase in SR membranes were depressed in the failing hearts. Likewise, Ca$\sp{2+}$-release channels, as monitored by $\sp3$H-ryanodine binding, and protein content were decreased in SR from failing hearts. These changes in the failing hearts were also associated with a depression in mRNA level for Ca$\sp{2+}$-pump in the failing hearts. Although gene expression for phospholamban, which regulates the SR Ca$\sp{2+}$-pump activity, was depressed in the failing heart, mRNA levels for calsequestrin, which binds Ca$\sp{2+}$ in the lumen, was unaltered. The observed alterations in the activities, protein content and gene expression for Ca$\sp{2+}$-pump was fully or partially prevented by treatment of infarcted animals with IMP. (Abstract shortened by UMI.)
URI: http://hdl.handle.net/1993/913
Appears in Collection(s):FGS - Electronic Theses & Dissertations (Public)

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