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 microns) were discussed out under microscope and mounted in a microvascular myograph for isometric tension recording. Experiments were designed to test compounds trophic to the small intestine, namely, epidermal growth factor, 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 and epidermal growth factor in concentrations up to 1 microM had no contractile or relaxant effects on the resistance arteries. The three short chain fatty acids alone and in combination, however, caused a concentration-dependent (range 0.1-30 mM) relaxation of resistance arteries precontracted with 50 mM KCl. This relaxant effect was significantly inhibited by the presence of the anion-exchange inhibitor 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid whereas it was unaffected by removal of the endothelium, presence of indomethacin, propranolol or phentolamine. These data suggest that the trophic effects of glutamine and epidermal growth factor on the small intestinal mucosa cannot be explained through actions on the resistance vasculature. In contrast, the relaxant effect of short chain fatty acid on resistance arteries in vitro suggests that these compounds may be able to improve the microcirculation in vivo. An improved microcirculation will, all things considered, facilitate the growth of the small intestinal mucosa.
Mortensen
F V
FV
Department of Gastrointestinal Surgery, Aarhus University Hospital, Denmark.
Nielsen
H
H
Aalkjaer
C
C
Mulvany
M J
MJ
Hessov
I
I
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D017920:Antiporters / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001158:Arteries / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005232:Fatty Acids, Volatile / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008833:Microcirculation; D009126:Muscle Relaxation / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009213:Myography
D017920:Antiporters; D004338:Drug Combinations; D005232:Fatty Acids, Volatile; D005973:Glutamine; D004815:Epidermal Growth Factor; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid