INTESTINAL REPERFUSION UP-REGULATES INDUCIBLE NITRIC-OXIDE SYNTHASE ACTIVITY WITHIN THE LUNG

Background. This study examines the hypothesis that pulmonary inducibl e nitric oxide synthase (iNOS) activity is regulated during intestinal reperfusion and that inhibition of NO generation exacerbates pulmonar y microvascular dysfunction. Methods Sprague-Dawley rats underwent int estinal ischemia and reperfusion (IIR) or sham operation (SHAM). Pulmo nary iNOS activity was measured by quantitating the conversion of L-ar ginine (L-Arg) to L-citrulline. Another set of animals undergoing IIR or SHAM received an inhibitor of NOS (N-G-nitro-L-arginine methylester ; L-NAME 20 mg/kg intravenously), substrate for NO generation (L-Arg; 300 mg/kg intravenously), or vehicle (normal saline solution; 3 ml). P ulmonary ty microvascular dysfunction was then quantitated by measurin g the extravasation of Evans blue dye (EBD) into the lung. Results. In ducible NOS activity was six times greater in the lungs of animals sus taining IIR when compared with SHAM (p = 0.0005). The concentration of EBD within the lungs of animals sustaining IIR was 30% greater than S HAM (p < 0.05). Inhibiting NOS with L-NAME significantly increased pul monary EBD concentration of both IIR and SHAM groups when compared wit h normal saline solution-treated animals (p < 0.0001). Treatment with L-Arg prevented this IIR-induced increase in pulmonary dye extravasati on. Conclusions. These data suggest that pulmonay iNOS activity is up- regulated in animals sustaining IIR and that this may serve as a compe nsatory protective response to remote organ injury.