Protective effects of inhibitors of nitric oxide synthase in immune complex-induced vasculitis


Wellcome Research Laboratories, Langley Court, South Eden Park Road, Beckenham, Kent BR3 3BS


  • 1The ability of analogues of l-arginine (N-iminoethyl-l-ornithine (l-NIO), NG-monomethyl-l-arginine (l-NMMA), NG-nitro-l-arginine methyl ester (l-NAME) and NG-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.
  • 2The 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 μm. For all other compounds, the IC50 values were > 5 mm.
  • 3The 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.
  • 4The protective effects of l-NIO were not associated with reductions in neutrophil accumulation, as measured by extraction from tissues of myeloperoxidase.
  • 5These 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.