TUBULAR EFFECTS OF ACETAMINOPHEN IN THE ISOLATED-PERFUSED RAT-KIDNEY

The effects of different acetaminophen (APAP) concentrations (1, 5 or 10 mM) on renal function were investigated in the isolated perfused ra t kidney (IPK). APAP was added to the perfusion media as a single dose after a equilibration time and control periods. Changes in fractional excretion of sodium (FE(Na)), water (FEH(2)O), glucose (FE(glu)) and in glomerular filtration rate (GFR) were measured. The lower concentra tion used only modified the FEH(2)O. APAP 10 mM induced an increment i n FEH(2)O (72% higher than control preparation), FE(Na) (79% higher th an control preparation) and an elevation in glucose excretion (55% hig her than control preparation), associated with a decrease in GFR (23% lower than control preparation). The influence of PGE(2) on the effect s of APAP was also investigated. PGE(2) prevented the APAP-induced dec rease in GFR and in glucose reabsorption, but did not change the patte rn of sodium and water handling. The effects of another vasodilator, v erapamil, on APAP-induced renal effects were also tested. Verapamil pr evented the glomerular but not the tubular effects of APAP. Urinary AP AP excretion data showed a similar availability of APAP to the tubular cells in all the groups. Our data suggest that APAP exerts a direct a ction in the IPK, affecting hemodynamic and tubular functions, and tha t the latter are not a consequence of hemodynamic alterations.