Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model.
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.
Hirata
Kunio
K
Department of Medicine, Shiga University of Medical Science, Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan.
Kume
Shinji
S
Araki
Shin-ichi
S
Sakaguchi
Masayoshi
M
Chin-Kanasaki
Masami
M
Isshiki
Keiji
K
Sugimoto
Toshiro
T
Nishiyama
Akira
A
Koya
Daisuke
D
Haneda
Masakazu
M
Kashiwagi
Atsunori
A
Uzu
Takashi
T
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*
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