The importance of mPGES1 in regulating renal function has been examined in mPGES1 deficient mice or by evaluating changes in its expression. However, it is unknown whether the prolonged mPGES1 inhibition induces significant changes of renal function when sodium intake is normal or low. This study examines the renal effects elicited by a selective mPGES1 inhibitor (PF-458) during 7 days in conscious chronically instrumented dogs with normal (NSI) or low (LSI) sodium intake. Results obtained in vitro and in vivo studies strongly suggest that PF-458 is a selective mPGES1 inhibitor. The administration of 2.4 mg/Kg/day of PF-458 to dogs with LSI did not induce significant changes in RBF and GFR. A greater dose of PF-458 (9.6 mg/kg/day) reduced RBF (P<0.05) but not GFR in dogs with LSI, and did not induce changes of renal hemodynamic in dogs with NSI. Both doses of PF-458 elicited a decrease (P<0.05) in PGE2 and an increase (P<0.05) in 6 KetoPGF1α. The administration of PF-458 did not induce significant changes in renal excretory function, plasma renin activity, and aldosterone and TXB2 plasma concentrations in dogs with LSI or NSI. The results obtained suggest that mPGES1 is involved in the regulation of RBF when sodium intake is low and that the renal effects elicited by mPGES1 inhibition are modulated by a compensatory increment in PGI2. These results may have some therapeutical implications since it has been shown that prolonged mPGES1 inhibition has lower renal effects than those elicited by NSAIDs or selective COX2 inhibitors.