Reversal of Cardiac Remodeling and Subcellular Defects by Prazosin in Heart Failure Due to Myocardial Infarction

Background: This study was undertaken to test if α-Adrenoceptor (AR) blockade with prazosin reverses cardiac remodeling and ameliorates subcellular defects in heart failure due to Myocardial Infarction (MI). Methods: Heart failure in rats was induced by MI for 12 wks and then treated with or without prazosin (10 mg/kg/ day) for 8 wks. Both control and experimental animals were assessed hemodynamically and echocardiographically for evaluating changes in heart function and cardiac remodeling, respectively. Left Ventricle (LV) was used for determining biomedical and molecular activities. Results: Cardiac dysfunction, as evident from depressed LV systolic pressure, rates of changes in pressure development and decay, cardiac output, ejection fraction and fractional shortening as well as increased LV end diastolic pressure, in 20 wks infarcted animals, was corrected partially by prazosin treatment. Different parameters of cardiac remodeling including increased LV posterior wall thickness and LV systolic diameter in failing hearts were fully or partially reversed whereas increased LV diastolic diameter was unaltered by prazosin therapy. Reversal of lung congestion and cardiac hypertrophy in MI animals by prazosin was associated with depression in the elevated levels of plasma norepinephrine, unlike epinephrine or dopamine. Depressions in Sarcoplasmic Reticular (SR) Ca2+-uptake activity as well as protein content for Ca2+-pump ATPase and phospholamban in failing hearts were reversed partially whereas depressed SR Ca2+-release activity and myofibrillar Ca2+-stimulated ATPase activity were not affected by prazosin. Alterations in mRNA levels for SR Ca2+-pump ATPase, SR Ca2+-release channels, and α-myosin heavy chain and β-myosin heavy chain in MI-induced heart failure were not influenced by prazosin treatment. Conclusions: It is suggested that the activation of α-AR system may be associated with cardiac remodeling and heart failure and the reverse cardiac remodeling by α-AR blockade may improve cardiac performance by attenuating defects in SR Ca2+-pump.