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Protective effects of inhibitors of nitric oxide synthase in immune complex‐induced vasculitis
Author(s) -
Mulligan M.S.,
Moncada S.,
Ward P.A.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb13423.x
Subject(s) - nitric oxide , arginine , myeloperoxidase , omega n methylarginine , immune system , chemistry , pharmacology , arginase , nitric oxide synthase , immune complex , immunology , medicine , biochemistry , inflammation , amino acid , organic chemistry
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 IC 50 value for l ‐NIO in the dermal vasculitis model was 65 μ m . For all other compounds, the IC 50 values were > 5 m m . 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.