EVIDENCE OF PEROXYNITRITE INVOLVEMENT IN THE CARRAGEENAN-INDUCED RAT PAW EDEMA

The role of peroxynitrite generated from nitric oxide and superoxide a nion was investigated in a model of acute inflammation induced by the injection of carrageenan into the rat hind paw. Paw edema was inhibite d 8 h following the administration of carrageenan by N-iminoethyl-L-ly sine (3-30 mg/kg, n = 6) or aminoguanidine (30-300 mg/kg, n = 6), two selective inhibitors of inducible nitric oxide synthase and by recombi nant human Cu/Zn superoxide dismutase coupled to polyethyleneglycol (1 2 X 10(3) U/kg, n = 6, P < 0.001). Moreover, at the same time point fo llowing carrageenan administration, intense immunoreactive staining fo r nitrotyrosine (a marker of peroxynitrite formation) was detected. Ou r results suggest that the generation of nitric oxide, superoxide anio n and peroxynitrite contributes to the edema observed in this acute mo del of inflammation.