N-monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats

Arthritis Rheum. 1994 Jul;37(7):1062-9. doi: 10.1002/art.1780370712.


Objective: To test the hypothesis that nitric oxide (NO) is involved in the pathophysiology of arthritis.

Methods: Arthritis was induced in male Lewis rats by the injection of adjuvant into the base of the tail. The NO synthase (NOS) inhibitor, NG-monomethyl-L-arginine (L-NMA), was administered daily by the oral route for 19 days. Paw swelling, plasma fibrinogen levels, and urinary NO2/NO3 levels were measured to assess the effect of L-NMA on the arthritic response and whole-body NO production, respectively. On day 20, the ankle joints were processed for histopathologic evaluation.

Results: The onset of clinical symptoms was preceded by elevated biosynthesis of NO. In a dose-dependent manner, L-NMA inhibited both NO biosynthesis and paw swelling; histopathologic changes in the ankle joints were also prevented. D-NMA had no effect on the development of arthritis, while L-arginine reversed the effects of L-NMA. Fibrinogen levels in rats with arthritis were unaffected by L-NMA.

Conclusion: NO is critical to the development of both the inflammatory and erosive components of adjuvant arthritis in rats. There may be a future clinical role for suitable inhibitors of NO production or activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors*
  • Animals
  • Arginine / analogs & derivatives*
  • Arginine / pharmacology
  • Arthritis, Experimental / etiology*
  • Arthritis, Experimental / urine
  • Disease Models, Animal
  • Male
  • Nitrates / urine
  • Nitric Oxide Synthase
  • Nitrites / urine
  • Rats
  • Rats, Inbred Lew
  • omega-N-Methylarginine


  • Nitrates
  • Nitrites
  • omega-N-Methylarginine
  • Arginine
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases