INTESTINAL REPERFUSION-INDUCED PULMONARY-EDEMA IS RELATED TO INCREASED PULMONARY INDUCIBLE NITRIC-OXIDE SYNTHASE ACTIVITY

Background. This study examines the hypothesis that specific inhibitio n of the inducible isoform of nitric oxide synthase (iNOS) will attenu ate intestinal reperfusion-induced pulmonary microvascular dysfunction . Methods. Sprague-Dawley rats underwent intestinal ischemia-reperfusi on (IR) or sham operation (SHAM). Before injury, the animals received a selective inhibitor of iNOS (S-methylisothiourea sulfate, SMT; L-N-6 [1-iminoethyl] lysine, L- NIL), a nonselective inhibitor of NOS (NG-n it ro-L-arginine methylester, L-NAME) or vehicle (0.9% saline). IR-ind uced changes in pulmonary microvascular permeability were assessed by quantitating the extravasation of Evans blue dye (EBD)-bound protein. into the lung. Pulmonary iNOS activity and content were assessed by ra diochemical analysis and Western blot, respectively. Results. There wa s 60% more EBD within the lungs of animals sustaining IR when compared with controls (P < .05). Pretreatment with SMT or L-NIL totally preve nted the increase in EBD extravasation associated with IR. In. contras t, pretreatment with L-NAME resulted in a 10% increase in dye extravas ation in those animals sustaining IR when compared with similarly inju red animals receiving saline (P > .05). There was significantly greate r iNOS activity and enzyme content within the lungs of animals sustain ing IR compared with controls. Conclusions. These data are consistent with the hypothesis that the release of nanomolar quantities of nitric oxide generated by iNOS co contributes to IR-induced pulmonary microv ascular dysfunction.