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 rat 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 (FE_H2O), glucose (FE_glu) and in glomerular filtration rate (GFR) were measured. The lower concentration used only modified the FE_H2O. APAP 10 mM induced an increment in FE_H2O (72% higher than control preparation), FE_Na (79% higher than control preparation) and an elevation in glucose excretion (55% higher than control preparation), associated with a decrease in GFR (23% lower than control preparation). The influence of PGE₂ on the effects of APAP was also investigated. PGE₂ prevented the APAP-induced decrease in GFR and in glucose reabsorption, but did not change the pattern of sodium and water handling. The effects of another vasodilator, verapamil, on APAP-induced renal effects were also tested. Verapamil prevented the glomerular but not the tubular effects of APAP. Urinary APAP excretion data showed a similar availability of APAP to the tubular cells in all the groups. Our data suggest that APAP exerts a direct action in the IPK, affecting hemodynamic and tubular functions, and that the latter are not a consequence of hemodynamic alterations. Received: 30 May 1994/Accepted: 19 August 1994