Cold restraint stress-induced gastric mucosal dysfunction role of nitric oxide

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 analogN ^G-nitro-l-arginie 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, whereasl-arginine, the substrate for nitric oxide, reversed the effect ofl-NAME. In an additional group of experiments, effects of cold-restraint stress andl-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, whereasl-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 thatl-NAME-induced alterations on mucosal permeability are not related to net transmucosal fluid flux and tissue neutrophils.Supported by a grant from the Turkish Scientific and Technical Research Council (TÜBITAK, TAG 1209).