Nitric Oxide Release in Response to Gut Injury

Abstract

We evaluated nitric oxide release in several models of intestinal inflammation through luminal nitrite concentrations. In anesthetized rabbits, piglets, and guinea pigs, luminal lavages were collected from loops of normal or injured small intestine. Lavages were analyzed spectrophotometrically for nitrite (Griess reagent) and protein. Myeloperoxidase (MPO) content of intestinal segments was used as an index of granulocyte infiltration and intestinal inflammation. Acute ileal inflammation was induced by luminal acetic acid + casein in rabbits and luminal deoxycholate in neonatal piglets and adult rabbits. Chronic ileitis was induced in guinea pigs by intraluminal trinitrobenzenesulfonic acid. In each model nitrite levels in ileal lavages were significantly greater than control loops/animals. Increased luminal protein and intestinal MPO activity paralleled the changes in nitrite levels. To determine whether nitric oxide production influenced mucosal repair, segments of ileum were perfused with the L-arginine antagonist NG-nitro-L-arginine methyl ester (L-NAME, 10 mg/ml) after acute acetic acid + casein exposure. L-NAME administration reversed the decline in epithelial permeability characteristic of epithelial restitution, causing an increase in epithelial permeability which was readily reversible. These results suggest that nitrite production is a useful index of gut injury and that nitric oxide may contribute to the functional repair of the epithelial barrier under acute conditions.

Significance of nitric oxide in the stimulation of intestinal fluid absorption in the rat jejunum in vivo

“…Corresponding with these results, castoroil-induced diarrhoea was prevented by administration of NO-synthase-inhibitors in an in vivo study (Mascolo et al, 1993). Conversely, inhibition of NO-synthase in vivo resulted in gastric and duodenal HCO3- (Takeuchi et al, 1993) and intestinal fluid secretion (Mourad et al, 1993;Miller et al, 1993a,b) and in an enhancement of intestinal epithelial permeability (Kubes, 1992;Miller et al, 1993c), thus pointing towards an antisecretory and/or proabsorptive role of NO in the intestine.…”

Gut and Liver

“…One possible mechanism could be the decreased perfusion of the small intestine because it has been shown that hypoxia induced by low flow conditions augments proinflammatory cytokine release from the liver and gut. [24][25][26][27][28] Moreover, preliminary results indicate that splenic and peritoneal macrophages from rats subjected to hypoxia express iNOS and release a large amount of NO 3 − /NO 2 − . Thus, the decreased blood flow in the liver, small intestine, and spleen after hemorrhage, as demonstrated in the present study (Table 2), may induce a local increase of cytokines that could, in turn, up-regulate iNOS expression, leading to a prolonged increase in tissue and plasma levels of NO 3 − /NO 2 − .…”

Assessment of the intestinal permeability after a gastrectomy and the oral administration of anticancer drugs in rats: Nitric oxide release in response to gut injury

“…After deproteinization, the total nitrite concentration was measured spectrophotometrically by the Griess reaction. 14 According to the method of Miller et al, 15 no attempt was made to convert the nitrate levels to nitrite to avoid any technical errors that may accompany the nitrate conversion process.…”