title: Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model.
abstract: The improvement of salt-sensitive hypertension is a therapeutic target for various vascular diseases. Glucagon-like peptide 1 (GLP-1), an incretin peptide, has been reported to have natriuretic effect as well as blood glucose lowering effect, although its exact mechanism and clinical usefulness remain unclear. Here, we examined anti-hypertensive effect of exendin-4, a GLP-1 analog, in salt-sensitive obese db/db mice and angiotensin II (angII)-infused C57BLK6/J mice. The treatment of exendin-4 for 12 weeks inhibited the development of hypertension in db/db mice. In db/db mice, the urinary sodium excretion was delayed and blood pressure was elevated in response to a high-salt load, whereas these were attenuated by exendin-4. In db/db mice, intra-renal angII concentration was increased. Furthermore, exendin-4 prevented angII-induced hypertension in non-diabetic mice and inhibited angII-induced phosphorylation of ERK1/2 in cultured renal cells. Considered together, our results indicate that exendin-4 has anti-hypertensive effects through the attenuation of angII-induced high-salt sensitivity.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan.
authors.forename: Kunio
authors.initials: K
authors.lastname: Hirata
authors.forename: Shinji
authors.initials: S
authors.lastname: Kume
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Araki
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Sakaguchi
authors.forename: Masami
authors.initials: M
authors.lastname: Chin-Kanasaki
authors.forename: Keiji
authors.initials: K
authors.lastname: Isshiki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugimoto
authors.forename: Akira
authors.initials: A
authors.lastname: Nishiyama
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koya
authors.forename: Masakazu
authors.initials: M
authors.lastname: Haneda
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Uzu
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006973:Hypertension / Q000139:chemically induced / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000096:biosynthesis; D017673:Sodium Chloride, Dietary / Q000009:adverse effects; D014688:Venoms / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D010455:Peptides; D018027:Receptors, Glucagon; D017673:Sodium Chloride, Dietary; D014688:Venoms; D000804:Angiotensin II; D000077270:Exenatide