N-MONOMETHYL ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE, SUPPRESSES THE DEVELOPMENT OF ADJUVANT ARTHRITIS IN RATS

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, N-G-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-MMA. 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.