Hormonal Mechanisms of Cardiac Remodeling in Heart Failure

Abstract

It is now generally accepted that cardiac dysfunction in congestive heart failure (CHF) is due to cardiac remodeling as a consequence of changes in the size and shape of the heart. Furthermore, both the sympathetic nervous system (SNS) and the renin-angiotensin system (RAS) are activated, and the circulating levels of catecholamines and angiotensin 11 are elevated in CHF. Experimental and clinical studies have revealed that the blockade of SNS by different adrenoceptor (AR) antagonists improve cardiac function and attenuate cardiac remodeling. In addition to modifying beta-AR-mediated signal transduction, beta-AR antagonists have been shown to depress the elevated levels of catecholamines in CHF. On the contrary, the improvement of cardiac function and cardiac remodeling in CHF due to the blockade of RAS by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers were associated with a reduction in the formation of angiotensin and antagonism of the angiotensin-receptor-mediated signal transduction, respectively. Blockade of either SNS or RAS prevented subcellular remodeling upon modifying changes in cardiac gene expression, reduced the development of intracellular Ca2+-overload, and attenuated the occurrence of oxidative stress in the failing heart. These observations are consistent with the view that the activation of both SNS and RAS plays a crucial role in the genesis of cardiac remodeling and cardiac dysfunction in CHF.