Modulation of adjuvant arthritis by endogenous nitric oxide

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Abstract
The role of endogenous nitric oxide (NO) in adjuvant arthritis in Lewis rats has been studied by use of l‐arginine, the amino acid from which NO is synthesized, and NG‐nitro‐l‐arginine methyl ester (l‐NAME), an inhibitor of NO synthase. Prolonged modulation (35 days) of the l‐arginine: NO pathway in rats was achieved by dissolving test compounds in the drinking water (l‐arginine: 3, 10 and 30 mg ml−1; l‐NAME: 0.1, 1 and 10 mg ml−1). Arthritis was exacerbated by l‐arginine and suppressed by l‐NAME in a dose‐related fashion. Combined treatment with l‐NAME (1 mg ml−1) and l‐arginine (30 mg ml−1) did not modify the arthritis. Reduced weight gain, which is a feature of adjuvant arthritis, was modified by these compounds so that l‐arginine reduced weight gain whereas l‐NAME increased weight gain compared with that in control animals. d‐Arginine (30 mg ml−1), NG‐nitro‐d‐arginine methyl ester (d‐NAME: 1 mg ml−1) and l‐lysine (30 mg ml−1), an amino acid not involved in the generation of NO, were without effect on either arthritis or body weight gain. . Antigen‐stimulated proliferation of T‐lymphocytes as well as generation of nitrite (NO2−) and release of acid phosphatase from macrophages were all enhanced in l‐arginine‐treated arthritic rats and reduced in l‐NAME‐treated animals. These results suggest that endogenous NO modulates adjuvant arthritis, possibly by interfering with the activation of T‐lymphocytes and/or macrophages.