Kaori Ito

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.

Neuronal Fos-like immunoreactivity associated with dexamethasone-induced hypertension in rats and effects of glucagon-like peptide-2.

AIMS Dexamethasone-induced hypertension models have been used to study the mechanisms of glucocorticoid-induced hypertension, but the role of glucocorticoids in central cardiovascular regulation is not clearly understood. In the present study, we investigated the sites associated with dexamethasone-induced hypertension in the central nervous system in rats. We further investigated whether glucagon-like peptide-2 (GLP-2) was effective for dexamethasone-induced hypertension. MAIN METHODS Male Sprague-Dawley rats were treated with saline or dexamethasone (0.03mg/kg/day, s.c) for 10days. GLP-2 (60μg/kg, i.v.) was given to rats after dexamethasone treatment. We measured systolic blood pressure by a tail-cuff method in conscious rats, and arterial blood pressure in anesthetized rats. Immunohisotochemical techniques were used to detection of the c-fos protein (Fos). KEY FINDINGS Fos-immunoreactivity (Fos-IR) in the dorsomedial hypothalamic nucleus (DMH) was higher in dexamethasone-treated rats than in saline-treated rats. However, Fos-IR in the infralimbic cortex, amygdala, and hippocampus was similar in saline-treated and dexamethasone-treated rats. Peripheral administration of GLP-2 reduced mean arterial blood pressure by 26%. After the peripheral administration of GLP-2, Fos-IR in the caudal ventrolatral medulla (CVLM) increased in dexamethasone-treated rats. SIGNIFICANCE Chronic dexamethasone treatment induced Fos-IR in the DMH. Peripheral administration of GLP-2 suppressed dexamethasone-induced hypertension in rats by enhancing inhibitory neuronal activity.