Brain renin-angiotensin-aldosterone system and ventricular remodeling after myocardial infarct: a review

After a myocardial infarct (MI), a variety of mechanisms contribute to progressive cardiac remodeling and dysfunction. Progressive activation of central sympathoexcitatory pathways appears to depend on a neuromodulatory pathway, involving local production of aldosterone and release of endogenous ouabain-like compounds ('ouabain') possibly from magnocellular neurons in the supraoptic and paraventricular nuclei. 'Ouabain' may lower the membrane potential of neurons and thereby enhance activity of angiotensinergic pathways. These central pathways appear to coordinate progressive activation of several peripheral mechanisms such as sympathetic tone and circulating and cardiac renin-angiotensin-aldosterone system (RAAS). Central blockade of aldosterone production, mineralocorticoid receptors, 'ouabain' activity, or AT1 receptors similarly prevents activation of these peripheral mechanisms. Cardiac remodeling after MI involves progressive left ventricular dilation, fibrosis, and decrease in contractile performance. Central blockade of this neuromodulatory pathway causes a marked attenuation of the remodeling and dysfunction, presumably by inhibiting increases in (cardiac) sympathetic activity and RAAS. At the cellular level, these systems may contribute to the cardiac remodeling by activating proinflammatory cytokines and cardiac myocyte apoptosis. New therapeutic approaches, specifically preventing activation of this brain neuromodulatory pathway, may lead to more optimal and specific approaches to the prevention of heart failure after MI.