Abstract
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; L-N 6-[1-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 IR 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. (Surgery 1998;124:457-63.)
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