Neurohumoral Mechanisms in Heart Failure: A Central Role for the Renin-Angiotensin System

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Abstract
Congestive heart failure (CHF) is often the result of a progressive deterioration in cardiac function associated with marked alterations in peripheral physiology. The neurohumoral mechanisms involved in these alterations have the paradoxical role of serving simultaneously as adaptive, compensatory changes and as major contributing elements in the progression of CHF. This review discusses some of the clinical and experimental data that describe the time course of these neurohumoral mechanisms, with an emphasis on the renin-angiotensin system (RAS). The central role of the RAS in the pathophysiology of heart failure is discussed in relation to its interaction with other neurohumoral systems, its role in the peripheral vascular alterations, and its role in the myocardial alterations in CHF. In addition, these effects are discussed in the context of both the circulating and local RAS and the ability of pharmacologic interventions that modulate the RAS to modify the course of CHF favorably, especially the angiotensin-converting enzyme (ACE) inhibitors. An understanding of the intricate interactions of these neurohumoral mechanisms in CHF has already led to the development of therapies that reduce morbidity and mortality and provides the basis for continuing advances in the treatment of CHF.