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Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

フォーマット:
論文
責任表示:
Ohtani, Keisuke ; Usui, Soichiro ; Kaneko, Shuichi ; Takashima, Shin-ichiro ; Kitano, Katsunori ; Yamamoto, Kanako ; Okajima, Masaki ; Furusho, Hiroshi ; Takamura, Masayuki
言語:
英語
出版情報:
Nature Publishing Group / Japanese Society of Hypertension, 2012-03-01
著者名:
Ohtani, Keisuke
Usui, Soichiro
Kaneko, Shuichi
Takashima, Shin-ichiro
Kitano, Katsunori
Yamamoto, Kanako
Okajima, Masaki
Furusho, Hiroshi
Takamura, Masayuki
続きを見る
掲載情報:
Hypertension Research
ISSN:
0916-9636  CiNii Research  Webcat Plus  JAIRO
巻:
35
通号:
3
開始ページ:
287
終了ページ:
294
バージョン:
author
概要:
Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T-and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30 min of left ascending coronary I/R. Benidipine was administered orally at 3 mg kg -1 daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2′ deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels. © 2012 The Japanese Society of Hypertension All rights reserved. 続きを見る
URL:
http://hdl.handle.net/2297/30372
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