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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1995 May;115(2):344–348. doi: 10.1111/j.1476-5381.1995.tb15883.x

Effect of nitric oxide on integrity, blood flow and cyclic GMP levels in the rat gastric mucosa: modulation by sialoadenectomy.

M A Tripp 1, B L Tepperman 1
PMCID: PMC1908316  PMID: 7545520

Abstract

1. The effects of the nitrosothiol, S-nitroso N-acetylpenicillamine (SNAP) which liberates nitric oxide (NO), on ethanol-mediated gastric damage, blood flow and cyclic GMP levels in siaoloadenectomized (SALX) rats have been investigated. 2. Intraluminal instillation of ethanol (5-50% w/v) dose-dependently induced haemorrhagic damage and decreased NO synthase activity in the gastric mucosa. Both the extent of mucosal damage and inhibition of NO synthase activity were exacerbated in SALX rats. 3. Epidermal growth factor administration (5 and 10 micrograms kg-1, s.c.) reduced mucosal damage but did not restore NO synthase activity in ethanol-treated SALX rats. 4. SNAP infusion (0.01-1.0 micrograms kg-1 min-1, i.v.) attenuated haemorrhagic damage in ethanol-treated rats. The reduction in mucosal damage was significantly greater in SALX rats. 5. SNAP administration also caused an increase in gastric mucosal blood flow and cyclic GMP levels in control rats and both responses were augmented in SALX animals. 6. These data suggest that SALX is associated with increases in mucosal susceptibility to ethanol-mediated damage and reduces mucosal NO synthase activity. Epidermal growth factor does not appear to influence mucosal NO synthase in ethanol-treated rats. Furthermore, SALX augments the responsiveness of the gastric mucosa to NO administration. Therefore, factors from the salivary glands influence gastric NO formation and mucosal responsiveness to a NO donor.

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Selected References

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  1. Andrews F. J., Malcontenti-Wilson C., O'Brien P. E. Protection against gastric ischemia-reperfusion injury by nitric oxide generators. Dig Dis Sci. 1994 Feb;39(2):366–373. doi: 10.1007/BF02090210. [DOI] [PubMed] [Google Scholar]
  2. Bodis S., Haregewoin A. Evidence for the release and possible neural regulation of nitric oxide in human saliva. Biochem Biophys Res Commun. 1993 Jul 15;194(1):347–350. doi: 10.1006/bbrc.1993.1826. [DOI] [PubMed] [Google Scholar]
  3. Boughton-Smith N. K., Hutcheson I. R., Deakin A. M., Whittle B. J., Moncada S. Protective effect of S-nitroso-N-acetyl-penicillamine in endotoxin-induced acute intestinal damage in the rat. Eur J Pharmacol. 1990 Dec 4;191(3):485–488. doi: 10.1016/0014-2999(90)94185-z. [DOI] [PubMed] [Google Scholar]
  4. Brown J. F., Keates A. C., Hanson P. J., Whittle B. J. Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells. Am J Physiol. 1993 Sep;265(3 Pt 1):G418–G422. doi: 10.1152/ajpgi.1993.265.3.G418. [DOI] [PubMed] [Google Scholar]
  5. COHEN S. Isolation of a mouse submaxillary gland protein accelerating incisor eruption and eyelid opening in the new-born animal. J Biol Chem. 1962 May;237:1555–1562. [PubMed] [Google Scholar]
  6. Chung S. J., Fung H. L. Relationship between nitroglycerin-induced vascular relaxation and nitric oxide production. Probes with inhibitors and tolerance development. Biochem Pharmacol. 1993 Jan 7;45(1):157–163. doi: 10.1016/0006-2952(93)90388-d. [DOI] [PubMed] [Google Scholar]
  7. EPSTEIN A. N., SPECTOR D., SAMMAN A., GOLDBLUM C. EXAGGERATED PRANDIAL DRINKING IN THE RAT WITHOUT SALIVARY GLANDS. Nature. 1964 Mar 28;201:1342–1343. doi: 10.1038/2011342a0. [DOI] [PubMed] [Google Scholar]
  8. Gysin B., Müller R. K., Otten U., Fischli A. E. Epidermal growth factor content of submandibular glands is increased in rats with experimentally induced gastric lesions. Scand J Gastroenterol. 1988 Aug;23(6):665–671. doi: 10.3109/00365528809093929. [DOI] [PubMed] [Google Scholar]
  9. Itoh M., Imai S., Joh T., Kawai T., Katsumi K., Yokochi K., Takeuchi T. Protection of gastric mucosa against ethanol-induced injury by intragastric bolus administration of epidermal growth factor combined with hydroxypropylcellulose. J Clin Gastroenterol. 1992;14 (Suppl 1):S127–S130. doi: 10.1097/00004836-199206001-00022. [DOI] [PubMed] [Google Scholar]
  10. Konturek S. J., Brzozowski T., Majka J., Pytko-Polonczyk J., Stachura J. Inhibition of nitric oxide synthase delays healing of chronic gastric ulcers. Eur J Pharmacol. 1993 Aug 3;239(1-3):215–217. doi: 10.1016/0014-2999(93)90997-v. [DOI] [PubMed] [Google Scholar]
  11. Konturek S. J., Dembinski A., Warzecha Z., Brzozowski T., Gregory H. Role of epidermal growth factor in healing of chronic gastroduodenal ulcers in rats. Gastroenterology. 1988 Jun;94(6):1300–1307. doi: 10.1016/0016-5085(88)90667-1. [DOI] [PubMed] [Google Scholar]
  12. Lopez-Belmonte J., Whittle B. J., Moncada S. The actions of nitric oxide donors in the prevention or induction of injury to the rat gastric mucosa. Br J Pharmacol. 1993 Jan;108(1):73–78. doi: 10.1111/j.1476-5381.1993.tb13442.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  14. Ogle C. W., Qiu B. S. Nitric oxide inhibition intensifies cold-restraint induced gastric ulcers in rats. Experientia. 1993 Apr 15;49(4):304–307. doi: 10.1007/BF01923407. [DOI] [PubMed] [Google Scholar]
  15. Olsen R. W., Snowhill E. W., Wamsley J. K. Autoradiographic localization of low affinity GABA receptors with [3H]bicuculline methochloride. Eur J Pharmacol. 1984 Mar 23;99(2-3):247–248. doi: 10.1016/0014-2999(84)90249-8. [DOI] [PubMed] [Google Scholar]
  16. Quintero E., Guth P. H. Nitric oxide-mediated gastric hyperemia decreases ethanol-induced gastric mucosal injury in uremic rats. Dig Dis Sci. 1992 Sep;37(9):1324–1328. doi: 10.1007/BF01295999. [DOI] [PubMed] [Google Scholar]
  17. Skinner K. A., Soper B. D., Tepperman B. L. Effect of sialoadenectomy and salivary gland extracts on gastrointestinal mucosal growth and gastrin levels in the rat. J Physiol. 1984 Jun;351:1–12. doi: 10.1113/jphysiol.1984.sp015227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Skinner K. A., Tepperman B. L. Influence of desalivation on acid secretory output and gastric mucosal integrity in the rat. Gastroenterology. 1981 Aug;81(2):335–339. [PubMed] [Google Scholar]
  19. Tepperman B. L., Kiernan J. A., Soper B. D. The effect of sialoadenectomy on gastric mucosal integrity in the rat: roles of epidermal growth factor and prostaglandin E2. Can J Physiol Pharmacol. 1989 Dec;67(12):1512–1519. doi: 10.1139/y89-244. [DOI] [PubMed] [Google Scholar]
  20. Tepperman B. L., Soper B. D. Effect of epidermal growth factor, transforming growth factor alpha and nerve growth factor on gastric mucosal integrity and microcirculation in the rat. Regul Pept. 1994 Feb 3;50(1):13–21. doi: 10.1016/0167-0115(94)90186-4. [DOI] [PubMed] [Google Scholar]
  21. Tepperman B. L., Soper B. D. Effect of sialoadenectomy on gastric mucosal integrity and growth in the rat. A time-course study. Dig Dis Sci. 1990 Aug;35(8):943–949. doi: 10.1007/BF01537241. [DOI] [PubMed] [Google Scholar]
  22. Tepperman B. L., Soper B. D. Interaction of nitric oxide and salivary gland epidermal growth factor in the modulation of rat gastric mucosal integrity. Br J Pharmacol. 1993 Sep;110(1):229–234. doi: 10.1111/j.1476-5381.1993.tb13797.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Tepperman B. L., Vozzolo B. L., Soper B. D. Effect of neutropenia on gastric mucosal integrity and mucosal nitric oxide synthesis in the rat. Dig Dis Sci. 1993 Nov;38(11):2056–2061. doi: 10.1007/BF01297085. [DOI] [PubMed] [Google Scholar]
  24. Tepperman B. L., Whittle B. J. Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation. Br J Pharmacol. 1992 Jan;105(1):171–175. doi: 10.1111/j.1476-5381.1992.tb14230.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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