Modulation of adjuvant arthritis by endogenous nitric oxide.
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 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). 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), 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. 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.
Ialenti
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A
Department of Experimental Pharmacology, University of Naples Federico II, Italy.
Moncada
S
S
Di Rosa
M
M
D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001169:Arthritis, Experimental / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D008239:Lysine / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D000135:Acid Phosphatase; D008239:Lysine; D019331:NG-Nitroarginine Methyl Ester