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.