Recent studies have shown that the disturbance of gastric mu- cosal microcirculation resulted in gastric mucosal ischemia, energy deprivation, and a decreased gastric mucosal barrier as well as an at- tenuation of mucosal restorative ability after injury might play a pathogenic role in the development of Acute Gastric Mucosal Lesion (AGML). Nitric oxide (NO) has been recently reported as a new gastroprotective factor related to protect stomach from many types of experimental damage. The main mechanism of its gastroprotec- ion has been contributed to its ability to maintain gastric mucosal microcirculation. But many questions has been raised as 1)the role of NO in AGML is debatable, 2)the mechanism of gastroprotection is controversial, 3) the effect of NO on gastric secretion is uncertain, 4) the relationship between NO and other gastro protective / de- structive mediators is in need of discernment, and 5)the expression of nitric oxide synthase (NOS) in gastric mucosa under stress is still lacking in study, therefore we conducted the present three experi- ments, employed two animal models of canine chambered stomach segment with intact vascular pedicle and AGML in rats induced by cold—restraint, to explore the answers to above questions. The first experiment investigated the role of endogenous NO in dog gastric mucosal injury induced by acidified aspirin solution. Ani- mals were divided into two groups: one group received N~G —nitro— L-arginine (L-NNA), which inhibits the biosynthesis of endoge- nous NO by competting with L-arginine (L-arg), the substrate for NO synthesis; another group pretreated with a large dose of L-arg, while similarly administered L-NNA, to restore the NO synthesis. Then the arterial pressure, gastric blood flow, transmucosal poten- tial differences, and the output of H~+ and gastric juice were mea- sured respectively. Ulcer index was also assessed after acidified as- pirin solution was administered. Results showed that, comparing with control study, L-NNA markedly elevated arterial pressure, in- tensified the gastric damage induced by aspirin (P<0. 01), de- creased transmucosal potential differences, and caused an evident fall in gastric blood flow (P<0. 05). Inhibition of NO had no effect on the secretion of gastric juice, whereas attenuated the gastric acid se- cretion stimulated by aspirin. Concurrent administration of L-arg absolutely reversed all of the above effects of L-NNA. This result suggests that endogenous NO is protective against the gastric mucosa from damage induced by acidified aspirin, and its protection may contribute to the preservation of gastric mucosal microcirculation. The second experiment evaluated the effect of endogenous NO on gastric mucosal injury induced by cold—restraint stress, and its relationship to the sulfhydryl compounds and lipid peroxidation of gastric mucosa in rats. After the gastric mucosal injury model in- duced by cold—restraint in rats was established, the study was com- pleted by: 1) viewing the effects of different doses of L-NNA (3. 125, 6. 25, 12. 5, 25, and 50mg/Kg) on gasric mucosal injury, 2) observing the roles of endogenous NO and sulfhydryl compounds in gastric mucosal damage, 3 ) measuring the alterations of gastric sulfhydryl compounds and malonaldehyde (MDA), the end product of lipid peroxidation in stressed rats, and 4) evaluating the effect of NO inhibition on tissue levels of sulfhydryl compounds and MDA in stressed gastric mucosa in rats. The results showed as follows. 1) The optimal dose of L-NNA used in this study was 12. 5mg/Kg. 2) Pretreatment with L-NNA (12. 5mg/Kg) or N— ethylmateimide (10mg/Kg, an inhibitor of endogenous sulfhydryl compounds) could either significantly intensify the gastric mucosal injury (P<0. 05). However, concurrent administration of L-arg, the substrate of NO, reduced the aggravation in mucosal damage caused by L-NNA. 3) After stress, the concentration of sulfhydryl compounds in the gastric mucosa was markedly decreased (P<0. 01), whereas MDA concentration was significantly enhanced (P<0. 05). 4)The inhibi- tion of endogenous NO by L-NNA had no effect on the concentra- tions of both sulfhydrl compounds and MDA in gastric mucosa of stressed rats. This set of experiments suggest that the endogenous NO could effectively protect the gastric mucosa from stress—induced damage in rats, and the protection role of NO is mediated neither by endogenous sulfhydryl compounds nor through lessening the extent of lipid peroxidation.

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