Influence of exogenous glucagon-like peptide 2 on mechanisms of enteric neurotransmitter-mediated vasorelaxation in the isolated bovine mesenteric artery and vein.
Glucagon-like peptide 2 (GLP-2) is getting more attention for its role in gut health and blood flow, but the exact mechanisms are still up for debate. A team from the University of Kentucky and the USDA just put out fresh data on how exogenous GLP-2 influences blood vessel relaxation in the bovine gut. They wanted to know: does GLP-2 directly relax blood vessels, or is it pulling strings behind the scenes?
Physiol Rep
by David GSS, Maples EC, Klotz JL et al.
“Influence of exogenous glucagon-like peptide 2 on mechanisms of enteric neurotransmitter-mediated vasorelaxation in the isolated bovine mesenteric artery and vein. David GSS(1), Maples EC(1), Klotz JL(2), Trotta RJ(1). Author information: (1)Department of Animal and Food Sciences, University of Kentucky, Lexington, Kentucky, USA. (2)Forage-Animal Production Research Unit, United States Department of Agriculture-Agricultural Research Service, Lexington, Kentucky, USA. Exogenous glucagon-like peptide 2 (GLP-2) administration increases small intestinal growth and mesenteric blood flow, although the vascular mechanisms involved remain unclear. The objective of this study was to characterize the effects of exogenous GLP-2 administration on glucagon-like peptide 2 (GLP-2)-, vasoactive intestinal peptide (VIP)-, serotonin (5-HT)-, and acetylcholine (ACh)-mediated vascular relaxation in isolated bovine mesenteric arteries (MA) and mesenteric veins (MV). Ten steers received repeated subcutaneous injections of bovine serum albumin or GLP-2 for 48 h before vessel collection. Vascular dimensions, vasoactive responses using myography, and mRNA expression of receptors associated with vasorelaxation were evaluated. Exogenous GLP-2 did not directly induce vasorelaxation in isolated MA or MV despite detectable GLP2R mRNA expression in both vessels, suggesting that GLP-2-mediated increases in mesenteric blood flow occur through indirect mechanisms. Vasoactive intestinal peptide induced dose-dependent vasorelaxation in both vessel types, and only VIPR2 mRNA was detected. Serotonin-mediated responses were not altered by exogenous GLP-2 treatment. In contrast, exogenous GLP-2 enhanced ACh-mediated vasorelaxation in the MA at greater agonist concentrations and increased NOS3 mRNA expression in the MV. These findings suggest that cholinergic signaling pathways may contribute to GLP-2-associated vasoregulation in the bovine MA. © 2026 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.”
Here’s what they did: Ten steers got either GLP-2 or a control injection for two days. Researchers then collected mesenteric arteries and veins—basically the main highways for blood to and from the gut. Using myography, they measured how these vessels reacted to four different signals: GLP-2 itself, vasoactive intestinal peptide (VIP), serotonin (5-HT), and acetylcholine (ACh).
What actually happened:
GLP-2 didn’t directly cause the vessels to relax, even though its receptor (GLP2R) was present. So, the direct effect is off the table.
VIP worked as expected, relaxing both arteries and veins in a dose-dependent way, but only one receptor (VIPR2) was involved.
Serotonin’s effects stayed steady regardless of GLP-2 exposure.
The interesting part: GLP-2 made acetylcholine-induced relaxation stronger in the arteries, especially at higher doses, and boosted NOS3 mRNA in the veins. That points to enhanced cholinergic signaling.
Key takeaway: GLP-2 isn’t acting alone. It’s not a direct vasodilator in this model, but it does seem to amplify the way acetylcholine relaxes blood vessels. Researchers looking at peptide-mediated vasoregulation might want to pay closer attention to these cholinergic pathways.
For those tracking new findings on gut peptides and vascular mechanisms, this study adds nuance to how GLP-2 fits into the picture. Check out the peptide research index for more on GLP-2 and related compounds. This kind of work keeps the research community moving forward.
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