Intestinal reperfusion-induced pulmonary edema is related to increased pulmonary inducible nitric oxide synthase activity

Background. This study examines the hypothesis that specific inhibition of the inducible isoform of nitric oxide synthase (iNOS) will attenuate intestinal reperfusion-induced pulmonary microvascular dysfunction. Methods. Sprague-Dawley rats underwent intestinal ischemia-reperfusion-(IR) or sham operation (SHAM). Before injury, the animals received a selective inhibitor of iNOS (S-methylisothiourea sulfate, SMT,' E-N⁶-[l-iminoethyl] lysine, L- NIL), a nonselective inhibitor of NOS (N(G)-nitro-L-arginine methylester, L- NAME) or vehicle (0.9% saline). IR-induced 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 radiochemical analysis and Western blot, respectively. Results. There was 60% more EBD within the lungs of animals sustaining IR when compared with controls (P <. 05). Pretreatment with SMT or L-NIL totally prevented the increase in EBD extravasation associated with IR. In contrast, pretreatment with L-NAME resulted in a 10% increase in dye extravasation in those animals sustaining IR when compared with similarly injured animals receiving saline (P >. 05). There was significantly greater iNOS activity and enzyme content within the lungs of animals sustaining lit compared with controls. Conclusions. These data are consistent with the hypothesis that the release of nanomolar quantities of nitric oxide generated by iNOS contributes to IR-induced pulmonary microvascular dysfunction.