Interplay Between the Mineralocorticoid System, Inflammation, Hypertension and Kidney Disease.

Abstract

Aldosterone, produced by adrenal glomerulosa cells, stimulated by angiotensin II (AngII), adrenocorticotrophin (ACTH) and potassium (K+), and inhibited by natriuretic peptides, plays a role in hypertension and CKD development and progression. Its effects are mediated by nuclear mineralocorticoid receptors (MRs) inducing genomic effects, and putatively by a membrane G-protein-coupled receptor which could be the G-protein-coupled estrogen receptor (GPER30), triggering non genomic actions. The classical effect of aldosterone is on the distal nephron to retain Na+ and water and excrete K+, contributing to electrolyte and extracellular volume control. However, aldosterone also acts by stimulating oxidative stress through different signaling pathways that include tyrosine kinases and mitogen-activated protein kinases to induce inflammation and fibrosis in blood vessels, the kidney and the heart. The actions of aldosterone also leads to endothelial dysfunction, which participates in its effects on target organs, including progression of hypertension. Blockade of MR or inhibition of aldosterone generation lowers blood pressure (BP) and protects target organs, reducing progression of CKD. All these actions are reviewed, with an emphasis on the effects on the kidney.