ID | 118690 |
タイトル別表記 | 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
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著者 |
モンフジャルカル, ウーガンツェツェグ
徳島大学大学院医学研究科(医学専攻)
Ganbaatar, Byambasuren
Tokushima University
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キーワード | Esaxerenone
Endothelial dysfunction
Mineralocorticoid receptor
Aldosterone
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資料タイプ |
学位論文
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抄録 | 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. |
掲載誌名 |
Journal of Atherosclerosis and Thrombosis
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ISSN | 18803873
13403478
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出版者 | Japan Atherosclerosis Society
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巻 | 30
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号 | 4
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開始ページ | 326
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終了ページ | 334
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発行日 | 2023-04-01
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備考 | 内容要旨・審査要旨・論文本文の公開
本論文は,著者Uugantsetseg Munkhjargalの学位論文として提出され,学位審査・授与の対象となっている。 |
権利情報 | 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 )
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EDB ID | |
出版社版DOI | |
出版社版URL | |
フルテキストファイル | |
言語 |
eng
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著者版フラグ |
博士論文全文を含む
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文科省報告番号 | 甲第3757号
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学位記番号 | 甲医第1582号
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学位授与年月日 | 2023-09-30
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学位名 |
博士(医学)
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学位授与機関 |
徳島大学
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部局 |
医学系
病院
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