Possible Underlying Mechanisms Responsible for Aldosterone and Mineralocorticoid Receptor–Dependent Renal Injury

There is increasing evidence indicating the roles of aldosterone and mineralocorticoid receptor (MR) in the pathogenesis of renal injury. In rats, chronic treatment with aldosterone and salt results in severe proteinuria and renal tissue injury, characterized by glomerulosclerosis and tubulointerstitial fibrosis. Aldosterone-induced renal tissue injury is associated with increases in reactive oxygen species (ROS) levels and activation of mitogen-activated protein kinases (MAPKs) or Rho-kinase. Treatment with a selective MR antagonist, eplerenone, prevents aldosterone-induced increases in ROS levels and MAPK activity and ameliorates renal injury. In vitro studies have revealed that MR is highly expressed in glomerular mesangial cells (RMCs), podocytes, and renal interstitial fibroblasts. In these renal cells, aldosterone induces cellular injury through NADPH oxidase-dependent ROS production and activation of…