Immunohistochemical determination of the site of hypotensive effects of glucagon-like peptide-2 in the rat brain

Proglucagon-derived glucagon-like peptide-2 (GLP-2) is released from enteroendocrine cells and neurons. GLP-2 regulates energy absorption and epithelial integrity in the gastrointestinal tract, but its effect on blood-pressure regulation remains unknown. In the present study, we found that GLP-2 administered both peripherally and centrally dose-dependently reduced mean arterial blood pressure (MAP) in male Wistar rats anesthetized with urethane and α-chloralose. Immunohistochemical detection of the c-fos protein (Fos) revealed that the peripherally and centrally administered GLP-2 induced Fos-immunoreactivity (Fos-IR) in the nucleus of the solitary tract (NTS) and the caudal ventrolateral medulla (CVLM). In contrast, Fos-IR in brainstem catecholamine neurons decreased after the administration of GLP-2. These results suggest that GLP-2 acts on specific brain nuclei to inhibit sympathetic nerve activity and this leads to hypotension.

► GLP-2 (i.v. and i.c.v.) reduced mean arterial blood pressure in anesthetized rats.
► Administered GLP-2 induced Fos-immunoreactivity in the NTS and CVLM.
► It also induced Fos-immunoreactivity of GABAergic neurons in the NTS, CVLM and PVH.
► GLP-2 may inhibit sympathetic nerve activity resulting in hypotention.