Vascular Mineralocorticoid Receptors Regulate Blood Pressure Effects on Myogenic Tone and Role in Aging

Abstract

Effects of aldosterone on blood pressure control have classically been attributed to sodium retention through its action on the kidney. However, increasingly it has been appreciated that aldosterone exerts effects directly on the vasculature. Here, we comment on novel data published recently that sheds light on new mechanisms, whereby aldosterone acting through the mineralocorticoid receptor on blood vessels, in interaction with angiotensin II and via oxidative stress and calcium channels, may affect age-associated changes in myogenic tone and exert effects on blood pressure regulation. Aldosterone is produced by the adrenal glomerulosa in response to angiotensin (Ang) II, elevated serum potassium, and corticotropin. It acts on the kidney to increase sodium reabsorption in the distal nephron interacting with the mineralocorticoid receptor (MR) and by activation of the apical epithelial sodium channel.1 In humans, primary hyperaldosteronism clearly establishes the role that aldosterone has on blood pressure (BP) and hypertension.2 However, in both normotensive subjects and in essential hypertension, contribution of aldosterone to BP has been more difficult to establish. In the Framingham study, quartiles of plasma levels of aldosterone were directly associated with BP.3 A fraction of patients with essential hypertension shows mild elevation of aldosterone plasma concentrations.4 On the contrary, treatment with MR antagonists lowers BP in human patients with essential hypertension,5 and particularly drug-resistant hypertension.6 Because aldosterone synthase inhibitors have similar effects as MR blockade in humans with hypertension,7 it is likely that the effects reported for MR antagonism are mediated by blockade of the action of aldosterone. On which organs does aldosterone act to raise BP? The initial answer is that it may in large measure do so by increasing sodium and water retention …