INCREASED LEVELS OF CIRCULATING NITRATES AND IMPAIRED ENDOTHELIUM-MEDIATED VASODILATION SUGGEST MULTIPLE ROLES OF NITRIC-OXIDE DURING ACUTEREJECTION OF PULMONARY ALLOGRAFTS

Experiments were designed to determine whether changes in pulmonary ar tery function could be reduced by treatment with a lipid peroxidation inhibitor (H 290/51) during acute rejection of pulmonary allografts. S ingle lung transplantation was performed in three groups of dogs: grou p 1 was maintained on immunosuppression for 8 days after operation (im munosuppressed, n = 5); in group 2, immunosuppression was discontinued on postoperative day 5, so that rejection occurred on postoperative d ay 8 (rejecting, n = 6); in group 3, immunosuppression was discontinue d after 5 days, and the lipid peroxidation inhibitor H 290/51 (25 mg/k g) was given perorally for 3 days (rejecting + H 290/51, n = 6). Plasm a nitric oxide (NOx) was measured by use of chemoluminescence. On post operative day 8 rejection was observed in groups 2 and 3. Contractions to angiotensin I and endothelium-dependent relaxations to adenosine d iphosphate were reduced in pulmonary arteries from rejecting lungs, Re sponses of rings from dogs treated with H 290/51 were similar to those from rejecting lungs. Rejection did not alter relaxations to exogenou s nitric oxide. However, plasma levels of NOx increased significantly during rejection independently of treatment with H 290/51. Results of this study confirm that endothelium-dependent relaxation of pulmonary arteries is reduced during acute rejection of lung allografts. The res ult extends these observations to suggest that treatment with a lipid peroxidation inhibitor neither protects the pulmonary artery function nor affects levels of circulating NOx. Therefore mechanisms other than lipid peroxidation participate in vascular changes associated with al lograft rejection.