Premium
Aldosterone increases renal expression of TGFβ in a rat model of acute cyclosporine nephrotoxicity (CsA‐Nx) (690.16)
Author(s) -
Ramírez Victoria,
Cruz Cristino,
Loredo Lilia,
Bobadilla Norma
Publication year - 2014
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.28.1_supplement.690.16
Subject(s) - aldosterone , medicine , endocrinology , mineralocorticoid receptor , spironolactone , endothelin 1 , endothelin receptor , creatinine , renal blood flow , kidney , chemistry , receptor
Previously, we demonstrated that spironolactone (mineralocorticoid receptor antagonist) prevented renal dysfunction and reduced structural injury (SI) in rats with chronic CsA Nx, suggesting a main role of aldosterone. This nephropathy however, is only induced in the rat when renin angiotensin aldosterone system (RAAS) is activated by a low salt diet. Here, we evaluated the aldosterone contribution in SI induced by CsA in absence of RAAS activation. Forty male Wistar rats were divided into: vehicle, aldosterone infused (Aldo, 0.7mg/Kg), CsA (5mg/Kg sc) and CsA+Aldo groups. All rats were fed with a standard salt diet and followed for 14 days. Mean arterial pressure, renal blood flow, creatinine clearance, were measured, as well as lipid peroxidation as an oxidative stress marker. mRNA and protein levels of TGFβ, pSMAD3/SMAD3, endothelin and endothelin receptors (ETA and ETB) were assessed. Hypoperfusion and renal dysfunction were observed in the three experimental groups, but only in CsA+Aldo group, oxidative stress, endothelin and TGFβ signaling were significantly increased. These results suggest that structural injury induced by CsA is at least in part, mediated by aldosterone in the absence of RAAS activation by a low sodium diet. Grant Funding Source : National council of science and technology of Mexico grants numbers 155700 to VRG and 181267 to NAB