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 s1 (TGF-s1), 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-s1, 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. CONCLUSION 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.
