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This Article Full Text Full Text (PDF) All Versions of this Article: 295/1/F73    most recent 00435.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Mathew, J. T. Articles by Singhal, P. C. PubMed PubMed Citation Articles by Mathew, J. T. Articles by Singhal, P. C.

Aldosterone induces mesangial cell apoptosis both in vivo and in vitro

¹Departments of Medicine, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park; ²Renmin Hospital of Wuhan University, Hubei, China; and ³Department of Pathology, New York Medical College, Valhalla, New York

Submitted 17 September 2007 ; accepted in final form 30 April 2008

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.

mesangial cells; apoptosis; aldosterone