BACKGROUND: The present study was performed to explore the effect of exogenous infusions of atrial natriuretic peptide (ANP) on the early inflammatory response during acute sodium overload in normal rats. METHODS: Sprague Dawley rats were exposed to acute sodium overload (Na 1.5 M). Nonhypotensive doses of ANP (1 and 5 microg x kg(-1) x h(-1)) were infused simultaneously with sodium or after sodium infusion in order to evaluate prevention or reversion of the inflammatory response, respectively. We determined inflammation markers in renal tissue by immunohistochemistry. RESULTS: Creatinine clearance was not reduced in any case. Sodium tubular reabsorption increased after sodium overload (334.3 +/- 18.7 vs. control 209.6 +/- 27.0 mEq x min(-1), p < 0.05) without changes in mean arterial pressure. This increase was prevented (228.9 +/- 26.4; p < 0.05) and reversed (231.5 +/- 13.9; p < 0.05) by ANP-5 microg x kg(-1) x h(-1). Sodium overload increased the expression of: RANTES (38.4.3 +/- 0.8 vs. 2.9 +/- 0.6%, p < 0.001), transforming-growth-factor-beta(1) (35.3 +/- 1.0 vs. 5.0 +/- 0.7%, p < 0.001), alpha-smooth muscle actin (15.6 +/- 0.7 vs. 3.1 +/- 0.3%, p < 0.001), NF-kappaB (9.4 +/- 1.3 to 2.2 +/- 0.5 cells/mm(2), p < 0.001), HIF-1alpha (38.2 +/- 1.7 to 8.4 +/- 0.8 cells/mm(2), p < 0.001) and angiotensin II (35.9 +/- 1.3 to 8.2 +/- 0.5%, p < 0.001). ANP-5 microg x kg(-1) x h(-1) prevented and reversed inflammation: RANTES (9.2 +/- 0.5 and 6.9 +/- 0.7, p < 0.001); transforming growth factor-beta(1) (13.2 +/- 0.7 and 10.2 +/- 0.5, p < 0.001) and alpha-smooth muscle actin (4.1 +/- 0.4 and 5.2 +/- 0.4, p < 0.001). Both prevention and reversion by ANP were associated with downregulation of NF-kappaB (3.2 +/- 0.4 and 2.8 +/- 0.5, p < 0.001) and angiotensin II (8.2 +/- 0.5 and 9.1 +/- 0.7, p < 0.001) and diminished hypoxia evaluated through HIF-1alpha expression (8.4 +/- 0.8 and 8.8 +/- 0.7, p < 0.001). CONCLUSION: Our study provides evidence supporting a protective role of ANP in both prevention and reversion of renal inflammation in rats with acute sodium overload.