PROTECTIVE EFFECTS OF INHIBITORS OF NITRIC-OXIDE SYNTHASE IN IMMUNE COMPLEX-INDUCED VASCULITIS

1 The ability of analogues of L-arginine (N-iminoethyl-L-ornithine (L-NIO), N(G)-monomethyl-L-arginine (L-NMMA), N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA)) to protect against inflammatory injury induced by activated neutrophils was investigated in rats following intradermal or intrapulmonary deposition of immune complexes. 2 The descending order of potency for protective effects of these analogues was: L-NIO > L-NMMA > L-NNA = L-NAME. The approximate IC50 value for L-NIO in the dermal vasculitis model was 65 muM. For all other compounds, the IC50 values were > 5 mM. 3 The protective effect of L-NIO in the skin was reversed in a dose-dependent manner by the presence of L-arginine, but not by D-arginine. L-Arginine also reversed the protective effects of L-NIO in immune complex-induced lung injury. 4 The protective effects of L-NIO were not associated with reductions in neutrophil accumulation, as measured by extraction from tissues of myeloperoxidase. 5 These data demonstrate that L-NIO has the most potent protective effects against immune complex-induced vascular injury induced by activated macrophages. Furthermore, they indicate that this injury is dependent upon the generation of nitric oxide.