Intestinal reperfusion up-regulates inducible nitric oxide synthase activity within the lung

Background. This study examines the hypothesis that pulmonary inducible nitric oxide synthase (iNOS) activity is up-regulated during intestinal reperfusion and that inhibition of NO generation exacerbates pulmonary microvascular dysfunction. Methods. Sprague-Dawley rats underwent intestinal ischemia and reperfusion (HR) or sham operation (SHAM). Pulmonary iNOS activity was measured by quantitating the conversion of l-arginine (L-Arg) to l-citrulline. Another set of animals undergoing HR 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). Pulmonary microvascular dysfunction was then quantitated by measuring the extravasation of Evans blue dye (EBD) into the lung. Results. Inducible NOS activity was six times greater in the lungs of animals sustaining HR when compared with SHAM ( p=0.0005). The concentration of EBD within the lungs of animals sustaining HR was 30% greater than SHAM (p