Premium
MINERALOCORTICOID RECEPTOR BLOCKADE PREVENTS RENAL ISCHEMIA‐REPERFUSION INJURY
Author(s) -
Ramírez Victoria,
MejíaVillet Juan Manuel,
Cruz Cristino,
Gamba Gerardo,
Bobadilla Norma A.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1219-c
Subject(s) - mineralocorticoid receptor , kidney , endocrinology , medicine , ischemia , spironolactone , oxidative stress , enos , renal blood flow , renal ischemia , acute tubular necrosis , reperfusion injury , receptor , chemistry , nitric oxide , aldosterone , nitric oxide synthase
We investigated whether spironolactone (Spiro) prevents the renal functional and structural damage induced by renal ischemia/reperfusion (I/R). Five groups of rats were studied, sham operated, rats underwent 20 min of ischemia and 24‐h of reperfusion, and three groups receiving Spiro 20 mg/k, 1, 2 or 3 days before I/R, respectively. I/R produced significant renal dysfunction and tubular damage. Spiro pre‐treatment completely prevented the decrease in renal blood flow and the development of acute renal failure in I/R groups. The protection conferred by Spiro was associated with decreased oxidative stress, as evidenced by a reduction in kidney lipoperoxidation, increased expression of antioxidant enzymes, and restoration of urinary NO2/NO3 excretion, that was accompanied by a reduction of tubular epithelial cell apoptosis. The eNOS expression was up‐regulated in I/R groups treated with Spiro, in addition to an increase in the activating phosphorylation of this enzyme at residue S1177 and a decrease in the inactivating phosphorylation at T497. In conclusion, our study shows that Spiro is a promising tool for renal protection against I/R, opening new therapeutic possibilities to prevent acute tubular necrosis in native and allograft kidneys.