A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice

• Material Type: 博士論文
• Title: A Selective Mineralocorticoid Receptor Blocker, Esaxerenone, Attenuates Vascular Dysfunction in Diabetic C57BL/6 Mice
• Author/Editor: Munkhjargal, Uugantsetseg; Fukuda, Daiju; Ganbaatar, Byambasuren; Suto, Kumiko; Matsuura, Tomomi; Ise, Takayuki; Kusunose, Kenya; Yamaguchi, Koji; Yagi, Shusuke; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka
• Author Heading: Munkhjargal, Uugantsetseg; Fukuda, Daiju; Ganbaatar, Byambasuren; Suto, Kumiko; Matsuura, Tomomi; Ise, Takayuki; Kusunose, Kenya; Yamaguchi, Koji; Yagi, Shusuke; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Sata, Masataka
• Publication, Distribution, etc.: Japan Atherosclerosis Society
• Publication Date: 2023-04-01
• Publication Date (W3CDTF): 2023-04-01
• Alternative Title: 選択的ミネラルコルチコイド受容体遮断薬であるエサキセレノンは糖尿病C57BL/6マウスの血管機能不全を抑制する; Effects of Esaxerenone on Diabetes-Induced Endothelial Dysfunction
• Periodical title: Journal of Atherosclerosis and Thrombosis
• No. or year of volume/issue: 30 4
• Volume: 30
• Issue: 4
• Pages: 326-334
• ISSN (Periodical Title): ISSN : 1880-3873; ISSN : 1340-3478
• Degree grantor/type: 徳島大学
• Date Granted: 2023-09-30
• Dissertation Number: 甲第3757号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Esaxerenone; Endothelial dysfunction; Mineralocorticoid receptor; Aldosterone
• Target Audience: 一般
• Note (General): Aims: Pharmacological blockade of mineralocorticoid receptors (MRs) is a potential therapeutic approach to reduce cardiovascular complications since MRs play a crucial role in cardiovascular regulation. Recent studies suggest that MR antagonists affect several extrarenal tissues, including vessel function. We investigated the effect of a novel nonsteroidal selective MR blocker, esaxerenone, on diabetes-induced vascular dysfunction. Methods: Diabetes was induced by a single dose of streptozotocin in 8-week-old male C57BL/6 mice. Esaxerenone (3 mg/kg/day) or a vehicle was administered by gavage to diabetic mice for 3 weeks. Metabolic parameters, plasma aldosterone levels, and parameters related to renal function were measured. Endothelium-dependent or -independent vascular responses of the aortic segments were analyzed with acetylcholine or sodium nitroprusside, respectively. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro study. Results: Induction of diabetes elevated plasma aldosterone level (P＜0.05) and impaired endothelium-dependent vascular relaxation (P＜0.05). The administration of esaxerenone ameliorated the endothelial dysfunction (P＜0.01) without the alteration of metabolic parameters, blood pressure, and renal function. Esaxerenone improved the eNOSSer1177 phosphorylation in the aorta obtained from diabetic mice (P＜0.05) compared with that in the vehicle-treated group. Furthermore, a major MR agonist, aldosterone, decreased eNOSSer1177 phosphorylation and increased eNOSThr495 phosphorylation in HUVECs, which recovered with esaxerenone. Esaxerenone ameliorated the endothelium-dependent vascular relaxation caused by aldosterone in the aortic segments obtained from C57BL/6 mice (P＜0.001). Conclusion: Esaxerenone attenuates the development of diabetes-induced endothelial dysfunction in mice. These results suggest that esaxerenone has potential vascular protective effects in individuals with diabetes.
• Access Restrictions: インターネット公開
• Rights (production): This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License.( https://creativecommons.org/licenses/by-nc-sa/4.0/deed.ja )
• Related Material (DOI): 10.5551/jat.63382
• Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• Original Data Provider (Database): 徳島大学 : 徳島大学機関リポジトリ

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http://repo.lib.tokushima-u.ac.jp/files/public/11/118690/20231024140035162936/k3757_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/118690/20231024140035314752/k3757_review.pdf fulltext

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