Exendin-4 has an anti-hypertensive effect in salt-sensitive mice model

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• 作者：Kunio Hirata ; Shinji Kume ; Shin-ichi Araki ; Masayoshi Sakaguchi ; Masami Chin-Kanasaki ; Keiji Isshiki ; Toshiro Sugimoto ; Akira Nishiyama ; Daisuke Koya ; Masakazu Haneda ; Atsunori Kashiwagi ; Takashi Uzu
• 关键词：Angiotensin II ; db/db mice ; Diabetic nephropathy ; Exendin-4 ; GLP-1 ; GLP-1 receptor ; Renin-angiotensin system ; Salt-sensitivity ; Hypertension ; Type 2 diabetes
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2009
• 出版时间：27 February 2009
• 年：2009
• 卷：380
• 期：1
• 页码：44-49
• 全文大小：334 K

文摘

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.