Abstract
The effects of 16,16-dimethyl prostaglandin E2 PGE2 on gastric mucosal blood flow and gastric mucosal damage were tested in rats given indomethacin. Blood flow was measured by hydrogen gas clearance. Indomethacin given intragastrically reduced the blood flow in nonlesion areas and the levels of PGE2 and 6-keto-PGF1α in the gastric mucosa and caused mucosal damage in a dose-related way. Indomethacin (20 mg/kg) significantly reduced the blood flow 30 min after administration, and the reduction increased until 90 min. Then the flow plateaued until 240 min. Gastric mucosal damage caused by 20 mg/kg of indomethacin and evaluated by only gross observations, began at 60 min and developed with time until 240 min after administration. 16,16-Dimethyl PGE2 (5 μg/kg) did not affect the reduction of blood flow caused by indomethacin during 240 min of measurements, but it significantly inhibited the indomethacin-induced mucosal damage evaluated by gross observations. These results suggest that prevention by 16,16-dimethyl PGE2 of grossly observed gastric mucosal damage caused by indomethacin was not related by preservation of the gastric mucosal blood flow in the areas without lesions.
Similar content being viewed by others
References
McGreevy JM, Moody FG: Protection of gastric mucosa against aspirin-induced erosions by enhanced blood flow. Surg Forum 28:357–359, 1977
Cheung LY: Topical effects of 16,16-dimethyl prostaglandin E2 on gastric blood flow in dogs. Am J Physiol 238:G514-G519, 1980
Miller TA, Henagan JM, Robert A: Effect of 16,16-dimethyl PGE2 on resting and histamine-stimulated gastric mucosal blood flow. Dig Dis Sci 25:561–567, 1980
Leung FW, Robert A, Guth PH: Gastric mucosal blood flow in rats after administration of 16,16-dimethyl prostaglandin E2 at a cytoprotective dose. Gastroenterology 88:1948–1953, 1985
Kobayashi K, Arakawa T, Satoh H, Fukuda T, Nakamura H: Effect of indomethacin, tiaprofenic acid, and dicrofenac on rat gastric mucosal damage and content of prostacyclin and prostaglandin E2. Prostaglandins 30:609–618, 1985
Whittle BJR: Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in rat. Gastroenterology 80:94–98, 1981
Konturek SJ, Kwiecien N, Obstulowicz W, Kiec-Dembinska A, Polanski M, Kopp B, Sito E, Olesky J: Effect of carprofen and indomethacin on gastric function, mucosal integrity and generation of prostaglandins in men. Hepatogastroenterology 29:267–270, 1982
Johansson C, Kollberg B, Nordeman R: Protective effect of prostaglandin E2 in the gastrointestinal tract during indomethacin treatment of rheumatic patients. Gastroenterology 78:479–493, 1980
Whittle BJR: Mechanisms underlying gastric mucosal damage induced by indomethacin and bile salts, and the actions of prostaglandins. Br J Pharmacol 60:455–460, 1977
Robert A, Nezamis JE, Lancaster C, Hanchar AJ: Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology 77:433–443, 1979
Leung FW, Guth PH, Scremin OU, Golanska EM, Kauffman GL Jr: Regional gastric mucosal blood flow measurements by hydrogen gas clearance in the anesthetized rat and rabbit. Gastroenterology 87:28–36, 1984
Arakawa T, Satoh H, Fukuda T, Nakamura H, Kobayashi K: Endogenous prostaglandin E2 in gastric mucosa of patients with alcoholic cirrhosis and portal hypertension. Gastroenterology 93:135–140, 1987
Arakawa T, Nakamura H, Fukuda T, Satoh H, Kobayashi K: Protection of isolated rat gastric cells by prostaglandin from damage caused by ethanol. J Clin Gastroenterol 10(suppl 1):S28-S34, 1988
Boughton-Smith NK, Vane JR, Whittle BJR: Effects of prostacyclin (PGI2), PGI2 and 6-keto-PGF1α on the rat gastric mucosa. Br J Pharmacol 62:413P, 1978
Gerber JG, Nies AS: Canine gastric mucosal vasodilation with prostaglandins and histamine analogs. Dig Dis Sci 27:870–874, 1982
Konturek SJ, Robert A: Cytoprotection of canine gastric mucosa by prostacyclin: Possible mediation by increased mucosal blood flow. Digestion 25:155–163, 1982
Gaskill HV III, Sirinek KR, Levine BA: Prostacyclin increases gastric mucosal blood flow via cyclic AMP. J Surg Res 33:140–145, 1982
Takeuchi K, Ueki S, Okabe S: Importance of gastric motility in the pathogenesis of indomethacin induced gastric lesions in rats. Dig Dis Sci 31:1114–1122, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Arakawa, T., Nakamura, H., Chono, S. et al. Absence of effect of 16,16-dimethyl prostaglandin E2 on reduction of gastric mucosal blood flow caused by indomethacin in rats. Digest Dis Sci 34, 1369–1373 (1989). https://doi.org/10.1007/BF01538071
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01538071