Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum: a detailed morphological study

Aliment Pharmacol Ther. 1995 Dec;9(6):605-13. doi: 10.1111/j.1365-2036.1995.tb00429.x.


Background: In indomethacin-induced jejunal ulceration in the rat, villi undergo both early microvascular injury and shortening that may involve activation of villous smooth muscle.

Aim: This study sought to substantiate light microscopic observations using three-dimensional imaging of early villous architectural changes in response to indomethacin.

Methods: At both 2 and 6 h after oral indomethacin 15 mg/kg or vehicle to groups of rats, the vasculature of the small intestine was visualised by both carbon-ink perfusion/confocal microscopy and injection casting. The mucosa was also examined for lesions by dissection microscopy and scanning electron microscopy.

Results: In indomethacin-dosed rats examined by scanning electron microscopy and histology, the mucosa at 2 h showed villous shortening and wrinkling of the surface epithelium without epithelial loss; at 6 h, the mucosa was flattened, often with epithelial loss to expose a 'contracted' villous core. Examination of the 'vasculature in carbon-injected tissues indicated significant reductions of both mucosal height and inter-capillary distance at both 2 and 6 h post-indomethacin. Scanning electron microscopy of injection casts at 2 and 6 h indicated similar changes. These changes were not seen in control tissues.

Conclusion: Histology, confocal microscopy and scanning electron microscopy support the proposal that villous shortening with disruption of surface capillary architecture are early changes in the ulcerative enteropathy induced by nonsteroidal anti-inflammatory drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Indomethacin / toxicity*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / ultrastructure
  • Jejunal Diseases / chemically induced*
  • Jejunal Diseases / pathology
  • Jejunum / blood supply
  • Jejunum / drug effects*
  • Jejunum / pathology
  • Male
  • Microcirculation / drug effects
  • Microcirculation / ultrastructure
  • Rats
  • Rats, Sprague-Dawley
  • Ulcer / chemically induced*
  • Ulcer / pathology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Indomethacin