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Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150), on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats
https://kagawa-u.repo.nii.ac.jp/records/357
https://kagawa-u.repo.nii.ac.jp/records/35795c83239-b36d-475b-badf-43e099bfabf8
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本文 (868.5 kB)
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内容の要旨 (45.4 kB)
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審査の結果の要旨 (471.4 kB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2019-04-24 | |||||
| タイトル | ||||||
| タイトル | Effects of the novel nonsteroidal mineralocorticoid receptor blocker, esaxerenone (CS-3150), on blood pressure and urinary angiotensinogen in low-renin Dahl salt-sensitive hypertensive rats | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||
| 資源タイプ | doctoral thesis | |||||
| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 著者 |
李, 磊
× 李, 磊 |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Abstract Herein, we studied the effects of the novel nonsteroidal selective mineralocorticoid receptor (MR) blocker, esaxerenone, on blood pressure and renal injury in Dahl salt-sensitive (DSS) rats. We also monitored intact urinary and total angiotensinogen (AGT). DSS rats were given a normal salt diet (NS: 0.4% NaCl, n = 10), a high-salt diet (HS: 8% NaCl, n = 10), HS + esaxerenone (1 mg/kg/day, p.o., n = 10), or HS + losartan (angiotensin II receptor blocker, 10 mg/kg/day, p.o., n = 10) for 6 weeks. Glomerular and tubulointerstitial tissues were obtained via a laser capture method. HS-treated DSS rats developed hypertension, albuminuria, and glomerular injury, which were associated with increased glomerular desmin staining and reduced mRNA levels of glomerular podocin and nephrin. HS-treated DSS rats also showed tubulointerstitial fibrosis with an increase in renal oxidative stress (4-hydroxynonenal staining). The urinary ((total AGT−intact AGT)/intact AGT) ratio, an indicator of intrarenal renin activity, was significantly suppressed in HS-treated DSS rats. Treatment with esaxerenone significantly decreased blood pressure, while losartan did not. Furthermore, esaxerenone attenuated the development of albuminuria, glomerular injury, and tubulointerstitial fibrosis more than losartan did, and this effect was associated with reduced renal oxidative stress. These data indicate that esaxerenone has antihypertensive and renal protective effects in salt-dependent hypertensive mice with suppressed intrarenal renin activity, as indicated by low levels of the urinary (total AGT−intact AGT)/intact AGT ratio. |
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| 言語 | en | |||||
| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士（医学） | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 16201 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 香川大学 | |||||
| 言語 | en | |||||
| 学位授与機関名 | Kagawa University | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2019-03-24 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第713号 | |||||
| 権利 | ||||||
| 言語 | en | |||||
| 権利情報 | Copyright © 2018, The Japanese Society of Hypertension | |||||
| 論文ID（NAID） | ||||||
| 識別子タイプ | NAID | |||||
| 関連識別子 | 500001345377 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 30587856 | |||||
| 関連サイト | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1038/s41440-018-0187-1 | |||||
| 関連サイト | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://dl.ndl.go.jp/pid/11279136 | |||||
| 著者版フラグ | ||||||
| 出版タイプ | P | |||||
| 出版タイプResource | http://purl.org/coar/version/c_fa2ee174bc00049f | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | Dahl salt-sensitive (DSS) rats | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | angiotensinogen (AGT) | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | esaxerenone | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | intrarenal renin activity | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| 主題 | nonsteroidal mineralocorticoid receptor (MR) blocker | |||||
| KEID | ||||||
| 値 | 28676 | |||||
