INHIBITION OF INDUCIBLE NITRIC-OXIDE SYNTHASE PROLONGS RAT LUNG ALLOGRAFT SURVIVAL

Nitric oxide (NO) has been demonstrated to be an important immunoregul ation molecule in the process of cellular immunologic interactions. Ou r recent results demonstrated that NO is produced in association with acute allograft rejection and NO inhibition may suppress rejection his tologically. This data provides direct evidence of NO in allograft rej ection and the immunosuppressive potential of NO inhibitors. In this p aper, the effect of NO inhibition on allograft survival was evaluated to investigate the capacity of NO inhibitors as immunosuppressive agen ts, Seventeen rat left lung transplants from BN donors to F344 recipie nts were accepted for this study. After surgery, recipients were rando mized into two groups and received either aminoguanidine (AG), a highl y selective NO synthase inhibitor, 200 mg/kg, intraperitoneal every 6h (n=13) or normal saline treatment (n=4). NO production was determined from the recipient's serum nitrite and nitrate levels. Graft survival was monitored via semiquantitative radiographic aeration scores (AS: 0 = opaque lung to 6 = normal appearing lung). The nitrite and nitrate levels were clearly detectable before the radiographic finding associ ated with rejection became obvious. Production of NO was significantly inhibited by AG treatment. AG treatment prolonged allograft survival radiographically (12.0 days and 6.0 days for treated and untreated gro ups respectively, p=0.0001). These data suggest that the inducible NO is produced in asociation with acute lung allograft rejection and may serve as a sensitive rejection marker. NO inhibition significantly pro longed rat lung allograft survival but failed to induce immunological tolerance.