Reverse Cardiac Remodeling in Heart Failure due to Myocardial Infarction by Some Pharmacologic Interventions

摘要

In view of the role of sympathetic nervous system and renin-angiotensin system in the pathogenesis of congestive heart failure, the blockade of adrenoceptors (AR) and angiotensin receptors (AT_1R) has been shown to attenuate cardiac remodelling and cardiac dysfunction during the development of heart failure. Recently, we have reported that cardiac performance abnormalities as well as cardiac remodelling due to myocardial infarction were partially reversed in animals with well-established heart failure by prazosin (an alpha-AR blocker), metoprolol (a beta-AR blocker) and losartan (an AT_1R antagonist) treatments. While lung congestion in these animals at advanced stages of heart failure was fully reversed, diastolic ventricular dilatation and elevated levels of plasma epinephrine were not affected by treatments with both AR-blockers and AT_1R antagonist. The elevated levels of plasma norepinephrine in animals with heart failure were partially reversed by prazosin and metoprolol treatments whereas losartan treatment further augmented the plasma levels of norepinephrine. These results suggest that partial reversal of cardiac remodelling and cardiac dysfunction by both alpha-AR and beta-AR blockers as well as AT_1R antagonists may be due to their inability to affect the elevated levels of plasma epinephrine in heart failure.