SHORT-CHAIN FATTY-ACIDS RELAX ISOLATED RESISTANCE ARTERIES FROM THE HUMAN ILEUM BY A MECHANISM DEPENDENT ON ANION-EXCHANGE

Ileal resistance arteries (internal diameter 184-337 mu m) were dissec ted out under microscope and mounted in a microvascular myograph for i sometric tension recording. Experiments were designed to test compound s trophic to the small intestine, namely, epidermal growth factor, glu tamine and the three short chain fatty acids, acetic, propionic and bu tyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM and epidermal growth factor in concentrations up to 1 mu M had no contractile or relaxant effects on the resistance arteries. Th e three short chain fatty acids alone and in combination, however, cau sed a concentration-dependent (range 0.1-30 mM) relaxation of resistan ce arteries precontracted with 50 mM KCl. This relaxant effect was sig nificantly inhibited by the presence of the anion-exhange inhibitor 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid whereas it was unaff ected by removal of the endothelium, presence of indomethacin, propran olol or phentolamine. These data suggest that the trophic effects of g lutamine and epidermal growth factor on the small intestinal mucosa ca nnot be explained through actions on the resistance vasculature. In co ntrast, the relaxant effect of short chain fatty acid on resistance ar teries iir vitro suggests that these compounds may be able to improve the microcirculation in vivo. An improved microcirculation will, all t hings considered, facilitate the growth of the small intestinal mucosa .