The β₃-Adrenoceptor Agonist CL316243 Prevents Indomethacin-Induced Jejunal Ulceration in the Rat

Abstract

It is now widely accepted that the small intestine is an important site of non-steroidal antiinflammatory drug (NSAID)-induced inflammation and ulceration (Aabakken, 1992; Bjarnason et al, 1993). We described a sequence of 4 histologically distinct and progressive phases of indomethacin-induced jejunal injury in the rat (Anthony et al, 1993. Nvgard et al, 1994). In particular, we noted that prior to neutrophil infiltration and mucosal necrosis, the villi underwent villous shortening, buckling of both the surface epithelium and underlying capillaries, and prominence of villus smooth muscle fibres. We hypothesised that villous shortening, as a consequence of villus smooth muscle contraction, was an early primary event that caused impedence of villous blood flow and ischaemic necrosis of the villous tip.