Skip to main content
Log in

Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost

Role of mucosal blood flow

  • Original Articles
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Pretreatment with sucralfate is known to protect gastric mucosa against the damaging effect of strong irritants, and this protection is accompanied by an increase in mucosal blood flow but the mechanisms underlying these effects have not been elucidated. Similar gastroprotective and hyperemic effects can be obtained with exogenous prostaglandins (PG), mild irritants such as dilute ethanol, and by capsaicin. In this study we investigated the role of nitric oxide (NO) in the prevention of ethanol-induced gastric damage and gastric blood flow by sucralfate, mild irritant such as 20% ethanol, capsaicin, and nocloprost, a stable PGE2 analog. Pretreatment withN G-nitro-l-arginine (l-NNA), an inhibitor of NO synthase, enhanced ethanol-induced mucosal damage and reduced dose-dependently the gastroprotective and hyperemic effects of sucralfate, dilute ethanol, and capsaicin. The doses ofl-NNA attenuating significantly the protective effects of sucralfate or 20% ethanol were 25–50 mg/kg, while those reducing the protection by capsaicin were 6.2–12.5 mg/kg. The attenuating effect ofl-NNA on gastroprotection was reversed byl-arginine but notd-arginine. For comparison, the gastroprotective (but not hyperemic) effect of nocloprost was not affected by the pretreatment withl-NNA and/or arginine. We conclude that sucralfate, mild irritant, and capsaicin activate the NO system that may contribute to their gastroprotective effect through enhancing mucosal circulation but that NO is not essential for the mucosal protection by PGE2 analog.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Konturek SJ, Radecki T, Piastucki I, Brzozowski T, Drozdowicz D: Gastroprotection by colloidal bismuth subcitrate (De-Nol) and sucralfate. Role of endogenous prostaglandins. Gut 28:201–205, 1984

    Google Scholar 

  2. Coleman JC, Lacz JP, Browne R-K, Dress DT: Effect of sucralfate or mild irritants on experimental gastritis and prostaglandin production. Am J Med 83(suppl 3B):24–30, 1987

    Google Scholar 

  3. Tarnawski A, Erickson RA: Sucralfate—24 years later; current concepts of its protective and therapeutic actions. Eur J Gastroenterol Hepatol 3:795–810, 1991

    Google Scholar 

  4. Hollander D, Tarnawski A, Gergely H, Zipser RD: Sucralfate protection of gastric mucosa against ethanol induced injury; a prostaglandin mediated process? Scand J Gastroenterol 19:97–102, 1984

    PubMed  Google Scholar 

  5. Holtzer P, Pabst A, Lippe IT: Intragastric capsaicin protects against aspirin-induced damage of gastric mucosa. Gastroenterology 96:1425–1433, 1989

    PubMed  Google Scholar 

  6. Holtzer P, Lippe IT: Stimulation of afferent nerve endings by intragastric capsaicin protects against ethanol-induced damage of gastric mucosa. Neuroscience 27:981–987, 1988

    PubMed  Google Scholar 

  7. Masayuki V, Yano S, Watanabe K: The role of capsaicin-sensitive afferent nerves in protective effect of capsaicin against absolute ethanol-induced gastric lesions in rats. Jpn J Pharmacol 55:279–282, 1991

    PubMed  Google Scholar 

  8. Peskar BM, Respondek M, Muller KM, Peskar BE: A role of nitric oxide in capsaicin-induced gastroprotection. Eur J Pharmacol 198:113–114, 1991

    PubMed  Google Scholar 

  9. Moncada S, Palmer RMJ, Higgs EA: Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142, 1991

    PubMed  Google Scholar 

  10. Whittle BJR, Lopez-Belmonte J, Moncada S: Regulation of gastric mucosal integrity by endogenous nitric oxide: interactions with prostanoids and sensory neuropeptides in the rat. Br J Pharmacol 198:607–611, 1990

    Google Scholar 

  11. Pique JM, Whittle BJR, Esplugues JV: The vasodilator role of endogenous nitric oxide in the rat gastric microcirculation. Eur J Pharmacol 174:293–296, 1989

    PubMed  Google Scholar 

  12. Tepperman BL, Whittle BJR: Endogenous nitric oxide and sensory neuropeptides interact in the modulation of the rat gastric microcirculation. Br J Pharmacol 105:171–175, 1992

    PubMed  Google Scholar 

  13. Robert A, Nezamis JE, Lancaster C, David JP, Fild SO, Hanchar AJ: Mild irritants prevent gastric necrosis through “adaptive cytoprotection” mediated by prostaglandins. Am J Physiol 245:G113-G121, 1983

    PubMed  Google Scholar 

  14. Svanes K, Gielason H, Guttu K, Herfjord JK, Fevang J, Gronbeck JK: Role of blood flow in adaptive protection of the cat gastric mucosa. Gastroenterology 100:1249–1258, 1991

    PubMed  Google Scholar 

  15. Hui WW, Chen BW, Cho CH, Luk CT, Lam SK: Role of gastric mucosal blood flow in gastroprotection. Digestion 48:113–120, 1991

    PubMed  Google Scholar 

  16. Hawkey CJ, Kemp RT, Walt RP, Bhaskar NK, Dawies J, Filipowicz B: Evidence that adaptive cytoprotection in rats is not mediated by prostaglandins. Gastroenterology 94:948–954, 1988

    PubMed  Google Scholar 

  17. Konturek SJ, Brzozowski T, Drozdowicz D, Krzyzek E, Garlicki J, Majka J, Dembinski A, Stachura J, Amon I: Nocloprost, a unique prostaglandin E2 analog with local gastroprotective and ulcer healing activity. Eur J Pharmacol 195:347–357, 1991

    PubMed  Google Scholar 

  18. Shepherd AP, Riedel GL, Kiel JW, Haumschild DJ, Maxwell LC: Evaluation of an infrared laser Doppler flowmeter. Am J Physiol 252:G832-G839, 1987

    PubMed  Google Scholar 

  19. Tarnawski A, Brzozowski T, Sarfeh IJ: Prostaglandin protection of human isolated gastric glands against indomethacin or ethanol. J Clin Invest 81:1081–1089, 1988

    PubMed  Google Scholar 

  20. Brzozowski T, Drozdowicz D, Majka J, Konturek SJ: Studies on gastroprotection induced by capsaicin and papaverine. J Physiol Pharmacol 43:309–322, 1992

    PubMed  Google Scholar 

  21. Holtzer P, Peskar BM, Peskar BA, Amman R: Release of calcitonin gene-related peptide induced by capsaicin in the isolated vascularly perfused rat stomach. Neurosci Lett 108:195–200, 1990

    PubMed  Google Scholar 

  22. Holtzer P, Guth PH: Neuropeptide control of rat gastric mucosal blood flow; increase by calcitonin gene-related peptide and vasoactive intestinal peptide but not substance P and neurokinin A. Circ Res 68:100–105, 1991

    PubMed  Google Scholar 

  23. Sharkey KA, Williams RG, Docray GJ: Sensory substance P innervation of the stomach and pancreas. Demonstration of capsaicin sensory neurons in the rat by combined immuno-histochemistry and retrograde tracing. Gastroenterology 87:914–922, 1984

    PubMed  Google Scholar 

  24. Sternini C, Reeve JR, Brecha N: Distribution and characterization of calcitonin gene-related peptide immunoreactivity in the digestive system of normal and capsaicin-treated rats. Gastroenterology 93:852–862, 1987

    PubMed  Google Scholar 

  25. Donc-Sheng LI, Raybould HE, Quintero E, Guth P: Calcitonin gene-related peptide mediates the gastric hyperemic response to acid back-diffusion. Gastroenterology 102:1124–1128, 1992

    PubMed  Google Scholar 

  26. Inshi KB, Chang B, Kerwin JF, Huang ZJ, Murad F:N w-nitro-L-arginine: A potent inhibitor of endothelium-derived relaxing factor formation. Eur J Pharmacol 176:219–223, 1990

    PubMed  Google Scholar 

  27. Radomski NW, Palmer RMJ, Moncada S: The antiaggregatory properties of vascular endothelium: Interactions between prostacyclin and nitric oxide. Br J Pharmacol 92:639–646, 1987

    PubMed  Google Scholar 

  28. Kubes P, Suzuki M, Granger DN: Nitric oxide: An endogenous modulator of leukocyte adhesion. Proc Natl Acad Sci USA 88:4651–4655, 1991

    PubMed  Google Scholar 

  29. Kvietys PR, Twohig B, Danzell J, Specian RD: Ethanol-induced injury to the rat gastric mucosa. Role of neutrophils and xantine oxidase-derived radicals. Gastroenterology 98:909–920, 1990

    PubMed  Google Scholar 

  30. Wallace JL, Keenan CM, Granger DN: Gastric ulcerations induced by nonsteroidal antiinflammatory drugs is a neutrophil-dependent process. Am J Physiol 259:G462-G467, 1990

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Konturek, S.J., Brzozowski, T., Majka, J. et al. Nitric oxide in gastroprotection by sucralfate, mild irritant, and nocloprost. Digest Dis Sci 39, 593–600 (1994). https://doi.org/10.1007/BF02088348

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02088348

Key words

Navigation