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

SUMMARY 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.