The renin-angiotensin system in left ventricular remodeling

Left ventricular remodeling is a dynamic process that occurs in reaction to an insult to the myocardium. The response to either loss of cells, as may occur following myocardial infarction, or to hemodynamic overload, as may occur in aortic stenosis, is an attempt to maintain cardiac output and normalize wall tension. This is accomplished through the activation of the renin-angiotensin system and hypertrophy of noninfarcted segments of the myocardium. in the case of moderate or large infarctions these mechanisms fail to normalize wall stress. The stimulus to further remodeling remains, viable myocytes hypertrophy (with greater increases in cell length than width), the mass-to-volume ratio increases, and an exponential increase in wall stress results. This increase in myocyte tension has been associated with premature myocyte cell death. Thus, a vicious cycle is established wherein overstretch of the myocardium while sustaining cardiac output leads to progressive myocyte loss and left ventricular dilation. The renin-angiotensin system plays an integral role in this process. Its inhibition by angiotensin-converting enzyme (ACE) inhibitors both chronically and immediately after myocardial infarction has been shown to decrease left ventricular volumes and reduce mortality. Controversy exists regarding the mechanism through which ACE inhibitors exert their effects. ACE inhibitors reduce afterload/preload, circulating angiotensin II levels, and raise circulating levels of bradykinin. It is not yet clear which mechanism is responsible for the greatest impact on left ventricular dilation and mortality. inhibition of the renin-angiotensin system is clearly beneficial to cardiac performance as well as morbidity and mortality when myocardium is lost and heart failure ensues. Specific modes of action require further definition, including local and systemic effects. Possible benefits of angiotensin receptor blockade versus augmentation of bradykinin requires definition, setting the stage for further study, while the beneficial therapeutic use of these agents continues.