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Short chain fatty acids dilate isolated human colonic resistance arteries
F V Mortensen1, H Nielsen, M J Mulvany
1Department of Surgery, Aarhus County Hospital, Denmark.
Abstract:
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.
Insights
Short chain fatty acids, but not glutamine, relax colonic resistance arteries. This vascular effect of short chain fatty acids may explain their beneficial impact on the gut microcirculation and intestinal mucosa.
Area of Science:
- Gastroenterology
- Vascular Biology
- Microcirculation Research
Background:
- Colonic resistance arteries play a crucial role in regulating gut blood flow.
- Glutamine and short chain fatty acids (SCFAs) are known trophic factors for the gastrointestinal tract.
- Understanding their vascular effects is key to explaining their physiological roles.
Purpose of the Study:
- To investigate the effects of glutamine and SCFAs (acetic, propionic, butyric acid) on colonic resistance artery tone.
- To determine if these compounds influence vascular smooth muscle or endothelial function.
- To explore potential mechanisms underlying the trophic effects of these compounds on the colon.
Main Methods:
- Colonic resistance arteries were isolated from human rectal carcinoma surgery specimens.
- Arteries were mounted in a microvascular myograph to measure isometric tension.
- Vascular responses to glutamine and SCFAs were assessed under various preconstricted conditions (K+, vasopressin) and with pharmacological inhibitors (indomethacin).
Main Results:
- Glutamine (up to 30 mM) had no significant effect on colonic resistance artery tone.
- Acetic, propionic, and butyric acids induced a concentration-dependent relaxation of preconstricted arteries.
- SCFA-induced relaxation was independent of endothelial function, indomethacin, and vasopressin-induced preconstriction.
Conclusions:
- The trophic effects of glutamine on the intestinal mucosa are unlikely mediated by direct actions on colonic resistance vasculature.
- SCFAs exert a direct relaxant effect on colonic resistance arteries in vitro.
- These findings suggest SCFAs may improve colonic microcirculation in vivo, potentially explaining their trophic influence on intestinal mucosa.
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