title: Cold restraint stress-induced gastric mucosal dysfunction. Role of nitric oxide.
abstract: 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.
authors.affiliation: Department of Physiology, Marmara University School of Medicine, Istanbul, Turkey.
authors.forename: T
authors.initials: T
authors.lastname: Coskun
authors.forename: B C
authors.initials: BC
authors.lastname: Yeğen
authors.forename: I
authors.initials: I
authors.lastname: Alican
authors.forename: O
authors.initials: O
authors.lastname: Peker
authors.forename: H
authors.initials: H
authors.lastname: Kurtel
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects; D003080:Cold Temperature / Q000009:adverse effects*; D004492:Edetic Acid / Q000493:pharmacokinetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical; D013237:Stereoisomerism; D013312:Stress, Physiological / Q000209:etiology / Q000503:physiopathology*
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D004492:Edetic Acid; D009195:Peroxidase; D019331:NG-Nitroarginine Methyl Ester