GLP-2 and GIP acutely increase superior mesenteric artery blood flow in male rats, and the effect is independent of nitric oxide and vasoactive intestinal peptide.

Following a meal, splanchnic blood flow increases. This is important for nutrient absorption and is regulated by the enteric nervous system and gastrointestinal (GI) hormones. Specifically, postprandial release of two GI hormones-glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) has been implicated in the regulation of splanchnic blood flow. We investigated the acute effects of GLP-2 and GIP alone or in combination on superior mesenteric artery blood flow in anesthetized rats using a transit-time flow probe and potential mediators of the GLP-2 and GIP effects using a nitric oxide (NO) synthase inhibitor and a vasoactive intestinal peptide (VIP) receptor antagonist. We also investigated the effects of a newly developed (human) GIP/GLP-2 receptor co-agonist and the effects of the GLP-2 receptor antagonist, GLP-2(3-33). Both GLP-2, GIP, and the co-agonist acutely increased superior mesenteric artery blood flow in anesthetized rats. The increase in blood flow was independent of the NO synthase inhibitor and VIP receptor antagonism. A synergistic effect of GLP-2 and GIP combined, or the GIP/GLP-2 receptor co-agonist, could not be demonstrated. GLP-2(3-33) effectively antagonized the GLP-2-induced increase in superior mesenteric artery blood flow. Our results establish GLP-2 and GIP as potent stimulators of superior mesenteric artery blood flow in anesthetized rats.