Influence of exogenous glucagon-like peptide 2 on mechanisms of enteric neurotransmitter-mediated vasorelaxation in the isolated bovine mesenteric artery and vein.

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.