Influence of acid and angiogenesis on kinetics of gastric ulcer healing in rats: interaction with indomethacin

Am J Physiol. 1995 Feb;268(2 Pt 1):G276-85. doi: 10.1152/ajpgi.1995.268.2.G276.


Indomethacin delays healing of experimental gastric ulcers. We investigated whether inhibition of gastric acid secretion by omeprazole or stimulation of angiogenesis by basic fibroblast growth factor (bFGF) may reverse this delay. Rats with gastric ulcers induced by cryoprobe were treated subcutaneously with either placebo, indomethacin (2 x 0.5 mg/kg), bFGF (2 x 100 micrograms/kg), omeprazole (1 x 40 mumol/kg), indomethacin plus omeprazole, or indomethacin plus bFGF given daily for 8, 10, 15, and 22 days. Ulcer size, epithelial cell proliferation, angiogenesis, and maturation of granulation tissue were sequentially quantified. Omeprazole significantly accelerated ulcer healing in an early phase (days 3-8). In contrast, bFGF accelerated healing in a late phase (days 10-15). Indomethacin significantly delayed ulcer healing in late phase and decreased prostaglandin generation, cell proliferation, angiogenesis, and maturation of granulation tissue. Despite stimulation of angiogenesis, bFGF did not reverse indomethacin-induced delay in ulcer healing. In contrast, omeprazole reversed indomethacin-induced effects on angiogenesis, cell proliferation, maturation of granulation tissue, and ulcer healing rate.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Bromodeoxyuridine / metabolism
  • Drug Combinations
  • Female
  • Fibroblast Growth Factor 2 / pharmacology
  • Gastric Acid / metabolism
  • Gastric Acid / physiology*
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / pathology
  • Gastrins / blood
  • Gastroscopy
  • Indomethacin / pharmacology
  • Kinetics
  • Neovascularization, Pathologic / metabolism*
  • Omeprazole / pharmacology
  • Prostaglandins / biosynthesis
  • Rats
  • Rats, Wistar
  • Stomach Ulcer / pathology
  • Stomach Ulcer / physiopathology*
  • Wound Healing / drug effects
  • Wound Healing / physiology*


  • Drug Combinations
  • Gastrins
  • Prostaglandins
  • Fibroblast Growth Factor 2
  • Bromodeoxyuridine
  • Omeprazole
  • Indomethacin