High-sodium diet promotes a profibrogenic reaction in normal rat kidneys: effects of Tempol administration.
BACKGROUND
Studies carried out in vitro have recently shown that salt loading induces an increasing mechanical stretch and a flow-induced superoxide production in the thick ascending limb of Henle's loop. In this regard, we hypothesized that the oxidative stress induced by salt overload could stimulate inflammatory and fibrogenic signaling pathways in normal rats.


METHODS
Sprague Dawley rats were fed with an 8% NaCl high- (HS) or 0.4% NaCl normal-salt (NS) diet for 3 weeks, with or without Tempol (T) administration (1 mM, administered in drinking water). Mean arterial pressure (MAP), glomerular filtration rate (GFR) and urinary sodium excretion (UVNa) were measured. NAD(P)H oxidase p47phox, angiotensin II (Ang II), transforming growth factor ß1 (TGF-ß1), a-smooth muscle actin (a-SMA) and nuclear factor-kappa B (NF-kB) expression were evaluated in renal tissues by immunohistochemistry.


RESULTS
A high NaCl diet produced a slight but significant increase in MAP and enhanced UVNa and oxidative stress. Administration of a high NaCl diet induced the overexpression of TGF-ß1, a-SMA and NF-?B in cortex and medulla, while Ang II increased in proximal convoluted tubules, and decreased in cortical collecting ducts. Tempol administration prevented these changes and simultaneously normalized MAP accompanied by an enhancement in GFR and UVNa.


CONCLUSIONS
The results showed that a high NaCl diet is able to produce a renal profibrotic response also in normal rats, which could be associated with oxidative stress rather than intrarenal Ang II expression.
Department of Pathophysiology, School of Pharmacy and Biochemistry, University of Buenos Aires, INFIBIOC-CONICET, Buenos Aires, Argentina. iroson@ffyb.uba.ar
María Inés
MI
Rosón
Silvana Lorena
SL
Della Penna
Gabriel
G
Cao
Susana
S
Gorzalczany
Marcela
M
Pandolfo
Carolina
C
Cerrudo
Belisario E
BE
Fernández
Jorge E
JE
Toblli
D000199:Actins / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D005355:Fibrosis; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007150:Immunohistochemistry; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage* / Q000652:urine; D013113:Spin Labels; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D000804:Angiotensin II; D000975:Antioxidants; D015415:Biomarkers; D003497:Cyclic N-Oxides; D019255:NADPH Oxidases; D016328:NF-kappa B; D017673:Sodium Chloride, Dietary; D013113:Spin Labels; D053773:Transforming Growth Factor beta1; C508962:Tgfb1 protein, rat; C498862:Acta2 protein, rat; C060505:neutrophil cytosolic factor 1; C001803:tempol