REVERSAL OF CARDIAC REMODELING IN HEART FAILURE BY ALPHA-ADRENOCEPTOR BLOCKADE


Naranjan S. Dhalla, Ph.D, M.D., MB, University of Manitoba, Winnipeg, Manitoba, Canada

In view of the role of elevated levels of circulating catecholamines, the activation of both alpha-adrenoceptor (AR) and beta-AR is considered to play a critical role in the pathogenesis of heart failure. Previous studies have shown the beneficial effects of beta-AR blockade in the failing heart; however, very little information on the action of alpha-AR blockade is available. In this study, heart failure in rats was induced by occluding the coronary artery for 12 weeks and then treated with or without prazosin (10 mg/kg/day) for 8 weeks. Depressed left ventricular (LV) systolic pressure, cardiac output and ejection fraction as well as LV diastolic pressure in 20 weeks infarcted animals were corrected partially by prazosin treatment. Cardiac hypertrophy and cardiac remodeling including increased LV posterior wall thickness in the failing hearts were also partially reversed by prazosin. The elevated levels of plasma norepinephrine and depressed sarcoplasmic reticular (SR) calcium pump activities were partially reversed whereas depressed SR calcium release and myofibrillar ATPase activities in heart failure were not affected by prazosin. The results suggest that partial reversal of cardiac remodeling and cardiac performance in heart failure by alpha-AR blockade was associated with partial reversal of SR calcium pump activity. (Supported by a grant from the Canadian Institutes of Health Research)