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 i n 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, pl asma fibrinogen levels, and urinary NO2/NO3 levels were measured to as sess the effect of L-NMA on the arthritic response and whole-body NO p roduction, respectively. On day 20, the ankle joints were processed fo r histopathologic evaluation. Results. The onset of clinical symptoms was preceded by elevated biosynthesis of NO. In a dose-dependent manne r, L-NMA inhibited both NO biosynthesis and paw swelling; histopatholo gic changes in the ankle joints were also prevented. D-NMA had no effe ct on the development of arthritis, while L-arginine reversed the effe cts of L-MMA. Fibrinogen levels in rats with arthritis were unaffected by L-NMA. Conclusion. NO is critical to the development of both the i nflammatory and erosive components of adjuvant arthritis in rats. Ther e may be a future clinical role for suitable inhibitors of NO producti on or activity.