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1 Medicine, Long Island Jewish medical Center, New Hyde Park, New York, United States; Medicine, North Shore University Hospital and Long Island Jewish Medical Center, New Hyde Park, New York, United States
2 Medicine, Long Island Jewish Medical Center, New Hyde Park, New York, United States
3 New Hyde Park, New York, United States; Medicine, Long Island Jewish medical Center, New Hyde Park, New York, United States
4 Medicine, Renmin Hospital Of Wuhan Univerisity, Wuhan, HuBei, China
5 Pathology, New York Medical College, Valhalla, New York, United States
6 Medicine, Renmin Hospital of Wuhan University, Hubei, China
7 Medicine, North Shore University Hospital and Long Island Jewish medical Center, Hyde Park, New York, United States
* To whom correspondence should be addressed. E-mail: pcsinghal{at}gmail.com.
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 as well as mitogenic effect on MCs. Aldosterone promoted MC apoptosis in a dose- and time-dependent manner. Spironolactone, a mineralocorticoid receptor (MR) antagonist, inhibited aldosterone-induced MC apoptosis. Similarly, antioxidants and free radical scavengers partially attenuated proapoaptotic effect 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 number of apoptosed mesangial cells. This proapoptotic effect of aldosterone was inhibited by eplerenone, a selective aldosterone antagonist. These findings suggest that aldosterone besides its hemodynamic effects may also be directly contributing to the occurrence of mesangial cell apoptosis.
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