Colonic biopsy specimens were obtained from patients undergoing surgery for carcinoma of the rectum. Colonic resistance arteries (internal diameter 178-345 microns) were dissected out under the microscope and mounted in a microvascular myograph capable of measuring isometric tension development. Experiments were designed to test compounds trophic to the gastrointestinal tract--namely, glutamine and the three short chain fatty acids, acetic, propionic, and butyric acid, for effects on vascular tone. Glutamine in concentrations up to 30 mM neither constricted nor dilated the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) dilatation of resistance arteries preconstricted with 50 mM K+, and this relaxant effect was unaffected by removal of the endothelium, presence of indomethacin, and preconstriction with vasopressin. These data suggest that the trophic effect of glutamine on intestinal mucosa cannot be explained through actions of this compound on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acids on resistance arteries in vitro suggests that these compounds may be able to improve the colonic microcirculation in vivo, thereby providing an explanation for their trophic effect on intestinal mucosa.