Modulation of adjuvant arthritis by endogenous nitric oxide

Br J Pharmacol. 1993 Oct;110(2):701-6. doi: 10.1111/j.1476-5381.1993.tb13868.x.


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.

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / physiopathology*
  • Cell Division / drug effects
  • Lysine / pharmacology
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / enzymology
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Rats
  • Rats, Inbred Lew
  • Spleen / cytology
  • Spleen / drug effects
  • T-Lymphocytes / drug effects
  • Weight Gain / drug effects


  • Nitric Oxide
  • Arginine
  • Acid Phosphatase
  • Lysine
  • NG-Nitroarginine Methyl Ester