Effect of N-G-nitro-L-arginine methyl ester on intestinal permeability following intestinal ischemia-reperfusion injury in a rat model

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenes is of necrotizing enterocolitis in premature infants. Previous studies sugg ested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuri es from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an inc rease in intestinal permeability in rats following IRI Sprague-Dawley rats weighing 200-300 g were divided into 4 groups: (1) untreated group (normal control); (2) ischemia-reperfusion group; (3) early NG-nitro-L-arginine met hyl ester (L-NAME), a specific inhibitor of NO production, treatment group, and (4) late L-NAME treatment group. Transient IRI was induced by 30-min o cclusion, followed by reperfusion of the isolated ileal loop. The L-NAME wa s administered 15 min before and after mesenteric ischemia as a 25-mg/kg bo lus. Fluorescein isothiocyanatedextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was n o significant increase in the portal vein FITC-D level among normal control s, ischemia-reperfusion group and late L-NAME-treated group, but there was an approximately 6-fold increase in the early L-NAME treatment group. The p athological features of the intestine following IRI include denudation of t he villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results sugg est that endogenous NO may play a role in the protecting intestinal integri ty after IRI. Copyright (C) 2001 S.Karger AG, Basel.