Back to Search
Start Over
Aldosterone induces mesangial cell apoptosis both in vivo and in vitro.
- Source :
-
American journal of physiology. Renal physiology [Am J Physiol Renal Physiol] 2008 Jul; Vol. 295 (1), pp. F73-81. Date of Electronic Publication: 2008 May 07. - Publication Year :
- 2008
-
Abstract
- 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.
- Subjects :
- Aldosterone blood
Animals
Antioxidants pharmacology
Blood Pressure drug effects
Creatinine blood
Cytochromes c metabolism
Eplerenone
Free Radical Scavengers pharmacology
Humans
In Situ Nick-End Labeling
Kidney Glomerulus cytology
Kidney Glomerulus drug effects
Male
Mesangial Cells cytology
Mineralocorticoid Receptor Antagonists pharmacology
Oxidative Stress
Proliferating Cell Nuclear Antigen metabolism
Rats
Rats, Sprague-Dawley
Spironolactone analogs & derivatives
Spironolactone pharmacology
bcl-Associated Death Protein metabolism
Aldosterone pharmacology
Apoptosis drug effects
Mesangial Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1931-857X
- Volume :
- 295
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Renal physiology
- Publication Type :
- Academic Journal
- Accession number :
- 18463316
- Full Text :
- https://doi.org/10.1152/ajprenal.00435.2007