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 MAPKs or Rho-kinase. Such aldosterone-induced renal cellular injury is markedly attenuated by treatment with eplerenone. These data suggest that aldosterone induces renal injury via activation of MR through mechanisms that cannot be simply explained by changes in blood pressure. In this review, we summarized recent findings on the roles of aldosterone and MR in the pathogenesis of renal injury with particular emphasis on potential underlying mechanisms.
Kiyomoto
Hideyasu
H
Department of CardioRenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University, Japan.
Rafiq
Kazi
K
Mostofa
Mahbub
M
Nishiyama
Akira
A
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D000077545:Eplerenone; D006801:Humans; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000503:physiopathology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism
D017382:Reactive Oxygen Species; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D054460:rho-Associated Kinases; D020928:Mitogen-Activated Protein Kinases