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How to best to counteract the enemies? By blocking neurohormonal activation

J. Soler-Soler* and D. García-Dorado

Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain

* Correspondence: Jordi Soler-Soler, MD, Servicio de Cardiología, Hospital Universitari Vall d'Hebron, P. vall d'Hebron, 119–129, 08035 Barcelona, Spain.

Abstract

Progression of heart failure is associated with an increased rate of cardiomyocyte apoptosis, and it has been hypothesized that this may, to an important extent, be due to neurhormonal activation. Experimental studies in cells and intact myocardium show that mild prolonged ischaemia, cytokine activation, and stimulation of G-protein-coupled receptors by adrenergic agonists and angiotensin II may trigger apoptotic cardiomyocyte death. However, the complex intracellular signal cascades that initiate apoptosis are not well understood but are inextricably superimposed on those that trigger hypertrophy. The net effect of neurohormonal activation on cardiomyocyte apoptosis is highly dependent on experimental conditions. In addition, recent studies support the existence of cardiomyocyte regeneration, rendering even more complex the relationship between increased apoptosis and net cell loss. In addition, other studies suggest that apoptotic cell loss may contribute to the regression of myocardial hypertrophy that is associated with certain treatments. The results of clinical studies are not consistent with a prominent role of apoptosis induced by neurohormonal activation in the progression of heart failure. neurohormonal activation in the progression of heart failure. Beta-blockers, inhibitors of the renin-angiotensin-aldosterone system and angiotensin receptor antagonists improve symptoms and prolong life, but are not able to prevent progression of heart failure. The hypothesis that the beneficial effect of blockade of neurohormonal activation in patients with heart failure is, to a significant extent, due to reduced cardiomyocyte apoptosis is still to be proven.

Key Words: ACE inhibitors • apoptosis • beta-blockers • heart failure • neurohormonal activation

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