Cold restraint stress-induced gastric mucosal dysfunction. Role of nitric oxide

Dig Dis Sci. 1996 May;41(5):956-63. doi: 10.1007/BF02091537.


The objectives of this study were to determine the cold restraint stress-induced changes in gastric mucosal permeability and to assess whether nitric oxide synthesis inhibition affects gastric mucosal integrity after cold-restraint administration. Cold-restraint stress caused multiple gastric lesions in 90% of animals. The lesion index was found to be 3.87 +/- 0.97 mm. Gastric mucosal permeability to the [51CR]EDTA molecule was significantly elevated in the cold-restraint group compared to control. In order to evaluate the role of nitric oxide in cold restraint stress-induced gastropathy, L-arginine analog NG-nitro-L-arginine methyl ester (L-NAME) was given as a bolus (10 mg/kg, intravenously) and infused at a rate of 2 mg/ml/hr for 2 hr after cold-restraint administration. L-NAME greatly exacerbated gastric mucosal dysfunction associated with cold-restraint stress. D-NAME, the biologically inactive enantiomer, did not enhance mucosal dysfunction, whereas L-arginine, the substrate for nitric oxide, reversed the effect of L-NAME. In an additional group of experiments, effects of cold-restraint stress and L-NAME on net transmucosal fluid flux as well as tissue myeloperoxidase activity (MPO) were assessed. Cold-restraint stress administration significantly reduced the absorptive capacity of stomach, whereas L-NAME treatment did not affect the stress-induced alterations on net fluid absorption. Furthermore, L-NAME treatment did not affect the cold restraint stress-induced changes in tissue MPO activity. Our results suggest that gastric barrier function is altered after cold-restraint stress and nitric oxide production is important in minimizing mucosal barrier dysfunction associated with cold-restraint stress administration. Our results also indicate that L-NAME-induced alterations on mucosal permeability are not related to net transmucosal fluid flux and tissue neutrophils.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine / analogs & derivatives
  • Arginine / pharmacology
  • Cell Membrane Permeability / drug effects
  • Cold Temperature / adverse effects*
  • Edetic Acid / pharmacokinetics
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / physiopathology*
  • Male
  • NG-Nitroarginine Methyl Ester
  • Nitric Oxide / physiology*
  • Peroxidase / drug effects
  • Peroxidase / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Restraint, Physical
  • Stereoisomerism
  • Stress, Physiological / etiology
  • Stress, Physiological / physiopathology*


  • Enzyme Inhibitors
  • Nitric Oxide
  • Arginine
  • Edetic Acid
  • Peroxidase
  • NG-Nitroarginine Methyl Ester