Characterization of the hypotensive effects of glucagon-like peptide-2 in anesthetized rats

Abstract

Glucagon-like peptide-2 (GLP-2) is a proglucagon-derived peptide released from enteroendocrine cells and neurons. We recently reported that GLP-2 induced hypotension. In the present study, we characterized the mechanisms of GLP-2-induced hypotension. GLP-2 was administered peripherally or centrally to male Wistar rats anesthetized with urethane and α-chloralose. The rats were vagotomized or systemically pretreated with atropine, prazosin, or propranolol before the GLP-2 administration. The central and peripheral administration of GLP-2 reduced mean arterial blood pressure (MAP). The maximum change of MAP (maximum ΔMAP) was reduced by vagotomy or prazosin, but not propranolol. The effects of the central but not peripheral administration of GLP-2 were reduced by atropine. These results suggest that GLP-2 modulates vagal afferent inputs and inhibits the sympathetic nervous system in the brain to induce hypotension.

Keywords: Blood pressure; CNS; CVLM; DMH; Fos-IR; GLP-2; IML; LC; MAP; NTS; PBS; RVLM; Sympathetic nervous system; Vagus; c-Fos immunoreativity; caudal ventrolateral medulla; central nervous system; dorsomedial hypothalamus; glucagon-like peptide-2; i.c.v.; i.v.; intermediolateral nucleus; intracerebroventricular; intravenous; locus coeruleus; mean blood pressure; nucleus solitary tract; phosphate-buffered saline; rostral ventrolateral medulla.