Abstract
Nitric oxide (NO) has been demonstrated to be an important immunoregulation molecule
in the process of cellular immunologic interactions. Our recent results demonstrated
that NO is produced in association with acute allograft rejection and NO inhibition
may suppress rejection histologically. This data provides direct evidence of NO in
allograft rejection and the immunosuppressive potential of NO inhibitors. In this
paper, the effect of NO inhibition on allograft survival was evaluated to investigate
the capacity of NO inhibitors as immunosuppressive agents. Seventeen rat left lung
transplants from BN donors to F344 recipients were accepted for this study. After
surgery, recipients were randomized into two groups and received either aminoguanidine
(AG), a highly selective NO synthase inhibitor, 200 mg/kg, intraperitoneal every 6
h (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
associated with rejection became obvious. Production of NO was signifi-cantly inhibited
by AG treatment. AG treatment prolonged allograft survival radiographically (12.0
days and 6.0 days for treated and untreated groups 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
prolonged rat lung allograft survival but failed to induce immunological tolerance.
Key words
Lung - Allograft - Transplantation - Rejection - Nitric oxide
