The brain renin-angiotensin-aldosterone system: a major mechanism for sympathetic hyperactivity and left ventricular remodeling and dysfunction after myocardial infarction.

Following a myocardial infarction (MI), increases in plasma angiotensin II may activate central nervous system (CNS) pathways and thereby peripheral mechanisms (eg, sympathetic activity and the circulating/cardiac renin-angiotensin-aldosterone system ). Plasma angiotensin II may directly activate CNS pathways through the subfornical organ and chronically enhance activity by way of a neuromodulatory system. The latter involves an increase in CNS aldosterone-causing "ouabain" release (eg, from magnocellular neurons of the supraoptic and paraventricular nuclei). "Ouabain" may lower membrane potential, thereby enhancing activity of angiotensinergic pathways. The resulting increases in sympathetic activity, and circulating/cardiac RAAS contributes to progressive left ventricular remodeling and dysfunction after MI and can be largely prevented by central administration of a blocker for any of the components of this neuromodulatory system. These new insights into the crucial role of the CNS may lead to new therapeutic approaches for the prevention of heart failure after MI with minimal peripheral adverse effects.