Inhibition of inducible nitric oxide synthase ameliorates functional and histological changes of acute lung allograft rejection

摘要: BACKGROUND We recently demonstrated that inhibition of inducible nitric oxide synthase (iNOS) ameliorated severe acute lung allograft rejection. This study used a rat transplant model to determine (1) the time course and cellular localization iNOS expression during histological progression unmodified rejection (2) whether prevented impaired gas exchange function and/or changes METHODS AND RESULTS mRNA enzyme activity were expressed in lungs mild, moderate, rejection, but not normal, isograft, or before mild allografts resulted elevated serum nitrite/nitrate levels, indicative increased vivo (NO) production. In situ hybridization infiltrating inflammatory cells, parenchymal cells. Allografts had significantly exchange, which was with selective inhibitor aminoguanidine (PaO2 566+/-19, 76+/-22, 504+/-105 mmHg for allograft, aminoguanidine-treated respectively; P<0.0002). Aminoguanidine also improved scores. CONCLUSIONS NO production occurred early stages persisted throughout process, localized cells; functional rejection; (3) production, detected by presence mRNA, protein, noninvasively measuring may serve as an marker