Aldosterone, the Mineralocorticoid Receptor and Mechanisms of Cardiovascular Disease

The mineralocorticoid receptor (MR) and aldosterone play a critical role in the regulation of plasma volume homeostasis and are critical for the control of normal physiological regulation blood pressure (BP) and organ perfusion and as a potent mediator of hypertension. Aldosterone and the MR also play a key role in regulating tissue volume expansion in many tissues, via the regulation of hypertrophy and/or hyperplasia of cardiac or vascular smooth muscle cells and through regulation of the extra cellular matrix (ECM) and tissue fibrosis. Over the last two decades since the Randomized ALdactone Evaluation Study (RALES) trial it has become apparent that increased MR signaling is much more than electrolyte homeostasis and plasma volume. RALES demonstrated a key protective effect of MRA in severe heart failure and stimulated significant new research to understand the actions of the MR and its ligands on the heart and vascular system, the outcomes of which will be discussed in this chapter.