Effect of N^G-Nitro-<i>L</i>-Arginine Methyl Ester on Intestinal Permeability following Intestinal Ischemia-Reperfusion Injury in a Rat Model

Abstract

Subclinical intestinal ischemia-reperfusion injury (IRI) causes an increase in mucosal permeability and may represent an early event in the pathogenesis of necrotizing enterocolitis in premature infants. Previous studies suggested that continuous, endogenous formation of nitric oxide (NO) maintains the mucosal integrity of the intestine, thus protecting the gut from injuries from blood-borne toxins and tissue-destructive mediators. This study was undertaken to assess whether the inhibition of NO production causes an increase 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 N^G-nitro-L-arginine methyl 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 occlusion, followed by reperfusion of the isolated ileal loop. The L-NAME was administered 15 min before and after mesenteric ischemia as a 25-mg/kg bolus. Fluorescein isothiocyanate-dextran (FITC-D) was used to quantitatively assess the alteration in mucosal permeability of the intestine. There was no significant increase in the portal vein FITC-D level among normal controls, 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 pathological features of the intestine following IRI include denudation of the villus epithelium and reduction of villus height, associated with marked inflammatory cell infiltration over the lamina propria. These results suggest that endogenous NO may play a role in the protecting intestinal integrity after IRI.

The effect of N G-nitro L-arginine methyl ester on colonic anastomosis after increased intra-abdominal pressure

“…In complete contrast with the current study and the others summarized above, L-NAME has also been linked with increased evidence of I/R injury in the intestine and in other organs like the brain and the liver [30][31][32][33]. Furthermore, Erbil et al [34] have reported decreased anastomotic healing in the obstructed colon after L-NAME.…”

“…In the current study, we preferred the intraperitoneal route to administer 2.5 mg/kg (approximately 0.625 mg per animal) L-NAME, which was the upper limit of the dose described by Takada et al [13]. In contrast, the studies quoted above [30][31][32][33][34] that generated unfavorable results with L-NAME used much higher doses and/or other routes.…”

Sodium Nitroprusside as a Nitric Oxide Donor in a Rat Intestinal Ischemia-Reperfusion Model

“…It inhibits both Ca 2+ dependent neuronal nitric oxide synthase (nNOS) and Ca 2+ independent inducible nitric oxide synthase (iNOS) 23. Luo et al reported that L-NAME reduces the I/R injury by inhibiting the endogenous NO 24.…”

The Immune-Enhancing Enteral Agents Arginine and Glutamine Differentially Modulate Gut Barrier Function following Mesenteric Ischemia/Reperfusion

“…Additionally, Luo et al administered N(G)-nitro-L-arginine methyl ester (L-NAME, a nitric oxide inhibitor) before and after a mild ischemic insult in rodents. 38 Animals receiving the nitric oxide inhibitor had increased permeability, suggesting that nitric oxide played a role in protecting intestinal barrier function after gut I/R. However, Ohtake et al demonstrated that arginine enhanced permeability in rabbit nasal epithelium.…”