Modulation of adjuvant arthritis by endogenous nitric oxide

Abstract

1 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 N^G-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). 2 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. 3 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. 4 d-Arginine (30 mg ml⁻¹), N^G-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. 5 . 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. 6 These results suggest that endogenous NO modulates adjuvant arthritis, possibly by interfering with the activation of T-lymphocytes and/or macrophages.