Selective inhibition of inducible nitric oxide in ischemia-reperfusion of rat small intestine

Purpose: We investigated the role of constitutive and inducible nitric oxid e (NO) synthases in intestinal ischemia-reperfusion (I/R) injury by observi ng the alterations in hemodynamics and intestinal microcirculation in respo nse to I/R in rats, with or without inhibitors of NO synthases. Methods: Adult male Sprague-Dawley rats (n = 9/group) received a standard T /R procedure alone: I/R plus intravenous administration of aminoguanidine t an inhibitor of inducible NO synthase I/R plus L-NAME (N(G)nitro-L-arginine methyl eater, an inhibitor of constitutive and inducible NO synthase); IR + L-Arg (L-arginine, an NO precursor); or a sham operation plus the vehicle . The I/R procedure was performed by clamping the perfusion vessels of a se gment of the terminal ileum, and medication was administered intravenously before and after intestinal ischemia. The intestinal perfusion and leukocyt e-endothelial interactions were evaluated with. in vivo microscopy and lase r Doppler flowmetry. Surface expression of CD11b (an adhesion molecule) of circulating granulocytes was measured with flow cytometry. Results: Intestinal I/R produced circulatory alterations, intestinal microc irculatory derangement, energy depletion, and lipid peroxidation. Aminoguan idine significantly attenuated the reperfusion-related depression of mean a rterial pressure (MAP), the decrease in intestinal perfusion index, the dec rease in tissue ATP preservation, the increase in tissue malondialdehyde (M DA) level, and the expression of CD11b of circulating granulocytes. Adminis tration of L-NAR IE had only minor and transient effects on reperfusion-rel ated changes of MAP, intestinal flux, numbers of adherent leukocytes, and C D11b expression, but had some protective effects on tissue MDA and adenosin e triphosphate levels and flow velocity. L-Arg further decreased the MAP bu t did not affect reperfusion-related variables. Conclusions: Our results show that the selective inhibition of inducible NO synthase by, aminoguanidine attenuates the hemodynamic and microcirculator y derangement that results from intestinal T/R.