The selective beneficial effects of nitric oxide inhibition in experimental colitis

Am J Physiol. 1995 Apr;268(4 Pt 1):G673-84. doi: 10.1152/ajpgi.1995.268.4.G673.

Abstract

We investigated the involvement of nitric oxide in trinitrobenzene-sulfonic acid (TNB) colitis. Every 24 h after TNB, rats were orally dosed with NG-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg), NG-nitro-D-arginine methyl ester (D-NAME), or water, and food intake, body weight, and plasma nitrite levels were measured. On day 6, colonic nitric oxide synthase and myeloperoxidase (MPO) activity, histology, intestinal muscle growth, NADPH-diaphorase, and myenteric nerve function were assessed. 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 MPO, and a fivefold elevation in plasma nitrite were measured. Smooth muscle hyperplasia and hypertrophy in both colonic muscle layers, numerous diaphorase-positive macrophages in the myenteric plexus, and a suppression of myenteric nerve function were also observed. Unlike D-NAME, oral L-NAME reduced MPO and intestinal muscle hyperplasia by > 90%. Likewise, plasma nitrite and colonic nitric oxide synthase were reduced by > 70%. L-NAME completely prevented macrophage infiltration into the muscle. Conversely, it had no effect on anorexia or intestinal smooth muscle hypertrophy, nor did it affect suppressed myenteric nerve neurotransmitter release. These results demonstrate the selective transmural protective effects of L-NAME in the inflamed colon, implicating nitric oxide as a mediator.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Oxidoreductases / antagonists & inhibitors
  • Amino Acid Oxidoreductases / metabolism
  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Body Weight
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology
  • Colon / enzymology
  • Colon / pathology
  • Eating
  • Hyperplasia
  • Hypertrophy
  • Intestines / innervation
  • Intestines / pathology
  • Male
  • Muscle, Smooth / innervation
  • Muscle, Smooth / pathology
  • Myenteric Plexus / physiopathology
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide Synthase
  • Norepinephrine / physiology
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Trinitrobenzenesulfonic Acid

Substances

  • Nitric Oxide
  • Trinitrobenzenesulfonic Acid
  • Arginine
  • Peroxidase
  • Nitric Oxide Synthase
  • Amino Acid Oxidoreductases
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine