THE SELECTIVE BENEFICIAL-EFFECTS OF NITRIC-OXIDE INHIBITION IN EXPERIMENTAL COLITIS

Citation
Cm. Hogaboam et al., THE SELECTIVE BENEFICIAL-EFFECTS OF NITRIC-OXIDE INHIBITION IN EXPERIMENTAL COLITIS, American journal of physiology: Gastrointestinal and liver physiology, 31(4), 1995, pp. 673-684
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Physiology
ISSN journal
0193-1857
Volume
31
Issue
4
Year of publication
1995
Pages
673 - 684
Database
ISI
SICI code
0193-1857(1995)31:4<673:TSBONI>2.0.ZU;2-C
Abstract
We investigated the involvement of nitric oxide in trinitrobenzenesulf onic acid (TNB) colitis. Every 24 h after TNB, rats were orally dosed with N-G-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), N-G-nitro-D -arginine methyl ester (D-NAME), or water, and food intake, body weigh t, and plasma nitrite levels were measured. On day 6, colonic nitric o xide synthase and myeloperoxidase (MPG) activity, histology, intestina l muscle growth, NADPH-diaphorase, and myenteric nerve function were a ssessed. Food intake and body weight were reduced during the first 72 h of colitis. On day 6 post-TNB, a fourfold increase in mucosal nitric oxide synthase, a 30-fold increase in MPG, and a fivefold elevation i n plasma nitrite were measured. Smooth muscle hyperplasia and hypertro phy in both colonic muscle layers, numerous diaphorase-positive macrop hages in the myenteric plexus, and a suppression of myenteric nerve fu nction were also observed. Unlike D-NAME, oral L-NAME reduced MPO and intestinal muscle hyperplasia by >90%. Likewise, plasma nitrite and co lonic nitric oxide synthase were reduced by >70%. L-NAME completely pr evented macrophage infiltration into the muscle. Conversely, it had no effect on anorexia or intestinal smooth muscle hypertrophy, nor did i t affect suppressed myenteric nerve neurotransmitter release. These re sults demonstrate the selective transmural protective effects of L-NAM E in the inflamed colon, implicating nitric oxide as a mediator.