Aldosterone induces mesangial cell apoptosis both in vivo and in vitro.
Both clinical and experimental reports indicate that aldosterone contributes to the progression of renal failure independent of its hemodynamic effects. In the present study, we evaluated effect of aldosterone on human mesangial cell (MC) growth. Aldosterone induced apoptotic and mitogenic effects on MCs. Aldosterone promoted MC apoptosis in a dose- and time-dependent manner. Spironolactone, a mineralocorticoid receptor antagonist, inhibited aldosterone-induced MC apoptosis. Similarly, antioxidants and free radical scavengers partially attenuated proapoaptotic effects of aldosterone. Aldosterone also enhanced dephosphorylation of phospho-Bad and accumulation of cytosolic cytochrome c in MCs. In in vivo studies, rats were randomly assigned to receive normal saline, aldosterone, or eplerenone + aldosterone for 28 days. Systolic blood pressure, urinary albumin excretion rate, serum creatinine, and aldosterone were measured. Aldosterone-infused rats developed elevated systolic blood pressure and albuminuria when compared with control rats. Aldosterone-treated rats also showed greater numbers of apoptosed MCs. This proapoptotic effect of aldosterone was inhibited by eplerenone, a selective aldosterone antagonist. These findings suggest that aldosterone, besides its hemodynamic effects, may also directly contribute to the occurrence of MC apoptosis.
Mathew
Jayant T
JT
Department of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, NY, USA.
Patni
Hitesh
H
Chaudhary
Ahmad N
AN
Liang
Wei
W
Gupta
Aakriti
A
Chander
Praveen N
PN
Ding
Guohua
G
Singhal
Pravin C
PC
D000450:Aldosterone / Q000097:blood / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D045304:Cytochromes c / Q000378:metabolism; D000077545:Eplerenone; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects*; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D018384:Oxidative Stress; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D051025:bcl-Associated Death Protein / Q000378:metabolism
D000975:Antioxidants; C494819:BAD protein, human; D016166:Free Radical Scavengers; D000451:Mineralocorticoid Receptor Antagonists; D018809:Proliferating Cell Nuclear Antigen; D051025:bcl-Associated Death Protein; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D045304:Cytochromes c; D003404:Creatinine