glucagon-like-peptide-2 and Hypertension

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.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Brain; Catecholamines; GABAergic Neurons; Glucagon-Like Peptide 2; Hypertension; Hypotension; Injections, Intraventricular; Male; Medulla Oblongata; Pressoreceptors; Rats, Inbred SHR; Rats, Inbred WKY; Tyrosine 3-Monooxygenase

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.. Male Sprague–Dawley rats were treated with saline or dexamethasone (0.03mg/kg/day, s.c) for 10 days. GLP-2 (60 μg/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. Immunohistochemical techniques were used to detection of the c-fos protein (Fos).. 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 ventrolateral medulla (CVLM) increased in dexamethasone-treated rats.. 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.

Topics: Animals; Arterial Pressure; Blood Pressure; Brain; Dexamethasone; Disease Models, Animal; Dorsomedial Hypothalamic Nucleus; Glucagon-Like Peptide 2; Glucocorticoids; Hypertension; Immunohistochemistry; Injections, Intravenous; Injections, Subcutaneous; Male; Neurons; Proto-Oncogene Proteins c-fos; Rats; Rats, Sprague-Dawley