Effects of centrally administered glucagon-like peptide-2 on blood pressure and barosensitive neurons in spontaneously hypertensive rats. (June 2018)

• Record Type: Journal Article
• Authors: Sasaki-Hamada, Sachie; Narusawa, Koji; Nakamura, Ryuji; Ishibashi, Hitoshi; Oka, Jun-Ichiro
• Is Part Of: Neuropeptides. Volume 69(2018)
• Page Start: 66
• Page End: 75
• Publication Date: 2018-06
• Subjects: A5 A5 catecholamine cell group -- Amb nucleus ambiguous -- AP area postrema -- CNS central nervous system -- CVLM caudal ventrolateral medulla -- DAB diaminobenzidine -- DMH dorsomedial hypothalamic nucleus -- Fos-IR Fos immunoreactivity -- GAD glutamic acid decarboxylase -- GLP-2 glucagon-like peptide-2 -- GLP-2R glucagon-like peptide-2 receptor -- ICV intracerebroventricular -- LC locus coeruleus -- MAP mean arterial blood pressure -- NTS nucleus of the solitary tract -- POMC pro-opiomelanocortin -- PVH paraventricular nucleus of the hypothalamus -- RVLM rostral ventrolateral medulla -- SHRs spontaneously hypertensive rats -- SHRSP stroke-prone SHR -- TH tyrosine hydroxylase -- VMH ventromedial hypothalamic nucleus -- WKY Wistar-Kyoto; (6): GLP-2 -- Hypotension -- Spontaneously hypertensive rats -- C-fos protein -- Immunohistochemistry -- Whole-cell recordings; Neuropeptides -- Periodicals; Neuropeptides; Neuropeptides -- Périodiques; Neuropeptides; Electronic journals; Periodicals; 572.65
• DOI: 10.1016/j.npep.2018.04.007
• Languages: English
• ISSNs: 0143-4179

Abstract

Abstract: The central administration of glucagon-like peptide-2 (GLP-2) decreases blood pressure in rats. In the present study, we investigated the hypotensive effects of GLP-2 using spontaneously hypertensive rats (SHRs), an animal model of hypertension. The central administration of GLP-2 (0.6 μg) decreased mean arterial pressure (MAP) in SHRs (−24.1 ± 4.5%; P < 0.05), but not in normotensive Wistar-Kyoto (WKY) rats (−10.6 ± 7.4%; P > 0.05), whereas GLP-2 (6 μg) decreased MAP in WKY rats (−23.5 ± 4.2%; P < 0.05) and SHRs (−46.7 ± 11.6%; P < 0.01) under anesthesia with urethane and α-chloralose. Histological analyses revealed that the central administration of GLP-2 (6 μg) induced Fos immunoreactivity ( Fos -IR) in the hypothalamic and medullary areas in WKY rats and SHRs. However, the distribution of Fos -IR in GABAergic neurons in the rostral ventrolateral medulla (RVLM) differed between WKY rats and SHRs. GLP-2 directly modulated the excitability of RVLM neurons in brainstem slices from SHRs, but not WKY rats. These results suggest that neuronal activity through the activation of GLP-2 receptors in the RVLM contributes to lowering blood pressure in SHRs. Highlights: The dose-dependent hypotensive effects of GLP-2 differed between WKY rats and SHRs. In SHRs, GLP-2 (ICV) increased GABAergic neuronal activity in the RVLM. In SHRs, GLP-2 (ICV) decreased catecholaminergic neuronal activity in the RVLM. GLP-2 directly modulated the excitability of RVLM neurons in SHRs, but not WKY rats.