Skip to main content
SpringerLink
Log in

Antiulcer drugs and gastric mucosal integrity

Effects of misoprostol, 16,16-dimethyl PGE2, and cimetidine on hemodynamics and metabolic rate in canine gastric mucosa

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

Abstract

Although prostaglandins (PGs) of the E series have gastric antisecretory and cytoprotective properties, many have different effects on the barrier integrity of the gastric mucosa. The direct effect of antiulcer drugs on gastric mucosal blood flow, mucosal barrier permeability, and metabolic rate have not been adequately studied. These factors are important in the defense of the gastric mucosa. Part of the difficulty relates to the possible influence of gastric mucosal blood flow on gastric acid secretion. To rule out this confounding factor, omeprazole can be used to reveal the true pharmacologic effects of these antiulcer drugs independent of the effect of gastric secretionper se. The study examined the effects of 16,16-dimethyl PGE2 (dmPGE2) misoprostol, and cimetidine on gastric mucosal blood flow, oxygen consumption, potential difference (PD), electrolytes, and fluid flux using theex vivo gastric chamber dog model. The PGs were administered intraluminally with an isotonic acid solution; cimetidine was administered by arterial infusion. None of the drug treatments had any significant effect on mean systemic arterial pressure, arterial blood gases, body temperature, or oxygen consumption. dmPGE2 significantly (P<0.001) decreased PD and enhanced the electrolytes (Na+, K+) and fluid flux across the mucosa (P<0.05). Misoprostol significantly increased gastric mucosal blood flow (P<0.02) and fluid efflux but decreased PD values. Cimetidine did not have any significant effects on barrier or metabolic functions of the stomach. These results suggest that a considerable difference exists in the pharmacology of gastric antisecretory drugs in relation to their effect on several factors affecting gastric mucosal integrity.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kauffman GL Jr: Blood flow and gastric secretion. Fed Proc 41:2080–2083, 1982

    Google Scholar 

  2. Moody FG, Durbin RP: Effects of glycine and other instillates on concentration of gastric acid. Am J Physiol 209:122–126, 1965

    Google Scholar 

  3. Londong W, Londong V, Cederberg C, Steffen H: Doseresponse study of omeprazole on meal-stimulated gastric acid secretion and gastrin release. Gastroenterology 85:1173–1178, 1983

    Google Scholar 

  4. Archibald LH, Moody FG, Simon MA: The measurement of gastric mucosal blood flow by radioactive microspheres. J Appl Physiol 38:1051–1056, 1975

    Google Scholar 

  5. Archibald LH, Moody FG, Simon MA: Comparison of gastric mucosal blood flow as determined by aminopyrine clearance and gamma-labeled microspheres. Gastroenterology 69:630–635, 1975

    Google Scholar 

  6. Rudolph AM, Heymann MA: The circulation of the fetusin utero: Methods for studying distribution of blood flow, cardiac output and organ blood flow. Circulation Res 21:163–184, 1967

    Google Scholar 

  7. SPSSx User's Guide. SPSS Inc. New York, McGraw-Hill, 1983, 806 pp

  8. Snedecor GW, Cochran WG: Statistical Methods. Ames, Iowa, Iowa State University Press, 1980, 507 pp

    Google Scholar 

  9. Moody FG: Gastric blood flow and acid secretion during direct intraarterial histamine administration. Gastroenterology 52:216–224, 1967

    Google Scholar 

  10. Larsen KR, Moody FG, Cheung LY: Controlled intragastric pH and cimetidine inhibition of histamine-stimulated gastric acid secretion in the dog. Surgery 89:196–201, 1981

    Google Scholar 

  11. Moody FG: Oxygen consumption during thiocyanate inhibition of gastric acid secretion in dogs. Am J Physiol 215:127–131, 1968

    Google Scholar 

  12. Cutting WC, Dodds EC, Noble RL, Williams PC: Pituitary control of alimentary blood flow and secretion. The effect of alterations in blood flow on gastric secretion. Proc R Soc Ser B 123:39–48, 1937

    Google Scholar 

  13. Jacobson ED, Linford RH, Grossman MI: Gastric secretion in relation to mucosal blood studied by a clearance technique. J Clin Invest 45:1–13, 1966

    Google Scholar 

  14. Lim RKS, Necheles H, Ni TG: Vasomotor reactions of the (vivi-perfused) stomach. Chin J Physiol 1:381–396, 1927

    Google Scholar 

  15. Thompson JE, Vane JR: Gastric secretion induced by histamine and its relationship to the rate of blood flow. J Physiol (London) 121:433–444, 1953

    Google Scholar 

  16. Ivarsson L, Darle N, Lundgren O: Effect of cimetidine on augmented gastric blood flow in duodenal ulcer patients. Gut 25:1093–1099, 1984

    Google Scholar 

  17. Polansky DB, Shirazi SS, Coon D: Lack of correlation of gastric acid secretion and blood flow. J Surg Res 26:320–325, 1979

    Google Scholar 

  18. Skarstein A, Svanes K, Soreide O, Vorhaug JE: Effect of pentagastrin on blood flow distribution in the stomach of cats with gastric ulcer. Scand J Gastroenterol 12:71–76, 1977

    Google Scholar 

  19. Varro V, Dobronte Z, Sagi I: Interrelation between gastric blood flow and HCl secretion in dogs. The basal condition and influence of secretory stimulants and vasoactive substances. Acta Med Acad Sci Hung 35:1–20, 1978

    Google Scholar 

  20. Perry MA, Haedicke GJ, Bulkley GB, Kvietys PR, Granger DN: Relationship between acid secretion and blood flow in the canine stomach: Role of oxygen consumption. Gastroenterology 85:529–534, 1983

    Google Scholar 

  21. Pawlik W, Tague LL, Tepperman BL, Miller TA, Jacobson ED: Histamine H1-and H2-receptor vasodilation of canine intestinal circulation. Am J Physiol 233:E219-E224, 1977

    Google Scholar 

  22. Curwain BP, Turner NC: The involvement of histamine receptor subtypes in gastric acid secretion and mucosal blood flow in the anesthetized rabbit. J Physiol (London) 311:431–442, 1981

    Google Scholar 

  23. Koo A:In vivo characterization of histamine H1-and H2-receptors in the rat stomach microcirculation. Br J Pharmacol 78:181–189, 1983

    Google Scholar 

  24. Salvati P, Whittle BJR: Vascular responses of the isolated perfused stomach of rabbit and rat to histamine. Eur J Pharmacol 89:63–68, 1983

    Google Scholar 

  25. Varhaug JE, Svanes K, Lekven J: Regional gastric blood flow and acid secretion during histamine H2 receptor blockade in cats. Scand J Gastroenterol 18:977–986, 1983

    Google Scholar 

  26. Mattsson H, Larsson H: Effects of omeprazole on gastric mucosal blood flow in the conscious rat. Scand J Gastroenterol 22:491–498, 1987

    Google Scholar 

  27. Zäch GA, Gyr KE, Alvensleben EV, Mills JG, Stalder GA, Dunn SL, Bloom S: A double-blind randomized, controlled study to investigate the efficacy of cimetidine given in addition to conventional therapy in the prevention of stress ulceration and haemorrhage in patients with acute spinal injury. Digestion 29:214–222, 1984

    Google Scholar 

  28. Konturek SJ, Robert A: Cytoprotection of canine gastric mucosa by prostacyclin: Possible mediation by increased blood flow. Digestion 25:155–163, 1982

    Google Scholar 

  29. Bálint GA, Sági I, Döbrönte Z, Varró, V: Effect of different prostaglandin analogues on gastric acid secretion and mucosal blood flow in the dog: Action on stimulated and resting mucosa. Acta Med Hung 41:149–155, 1984

    Google Scholar 

  30. Arvidsson S, Haglund U: On the pathogenesis of acute gastric mucosal lesions in septic shock. Scand J Gastroenterol 105(suppl):67–74, 1984

    Google Scholar 

  31. Larsen KR, Jensen NF, Davis EK, Jensen JC, Moody FG: The cytoprotective effects of (±)-15-deoxy-16-α,β-hydroxy-16-methyl PGE1 methyl ester (SC-29333) versus aspirinshock gastric ulcerogenesis in the dog. Prostaglandins 21(suppl):119–124, 1981

    Google Scholar 

  32. Dajani EZ, Callison DA, Bertermann RE: Effects of E-prostaglandins on canine gastric potential difference. Dig Dis Sci 23:436–442, 1978

    Google Scholar 

  33. Colton DG, Callison DA, Dajani EZ: Effects of prostaglandin E1 derivative, SC-29333, and aspirin on gastric ionic fluxes and potential difference in dogs. J Pharmacol Exp Ther 210:283–288, 1979

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine and Surgery, School of Medicine, University of Utah, Salt Lake City, Utah

    Kenneth R. Larsen PhD, Esam Z. Dajani PhD & Martha M. Ives MD

  2. Searle Laboratories, Chicago, Illinois

    Kenneth R. Larsen PhD, Esam Z. Dajani PhD & Martha M. Ives MD

Authors
  1. Kenneth R. Larsen PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Esam Z. Dajani PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martha M. Ives MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

This study was supported by the National Institutes of Health grant GM23095 and by the University of Utah.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Larsen, K.R., Dajani, E.Z. & Ives, M.M. Antiulcer drugs and gastric mucosal integrity. Digest Dis Sci 37, 1029–1038 (1992). https://doi.org/10.1007/BF01300283

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01300283

Key Words

Search

Navigation