MISC

2006年9月

Effects of adrenomedullin on cardiac oxidative stress and collagen accumulation in aldosterone-dependent malignant hypertensive rats

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
  • Matlubur Rahman
  • ,
  • Akira Nishiyama
  • ,
  • Peng Guo
  • ,
  • Yukiko Nagai
  • ,
  • Guo-Xing Zhang
  • ,
  • Yoshihide Fujisawa
  • ,
  • Yu-Yan Fan
  • ,
  • Shoji Kimura
  • ,
  • Naohisa Hosomi
  • ,
  • Koji Omori
  • ,
  • Youichi Abe
  • ,
  • Masakazu Kohno

318
3
開始ページ
1323
終了ページ
1329
記述言語
英語
掲載種別
DOI
10.1124/jpet.106.105106
出版者・発行元
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS

We examined the effects of adrenomedullin on cardiac oxidative stress and collagen accumulation in aldosterone-dependent malignant hypertensive rats. Spontaneously hypertensive rats (SHRs) were treated with one of the following combinations for 4 weeks: tap water and vehicle [ 0.5% ethanol, subcutaneously (s.c.), n = 5], 1% NaCl in drinking water and vehicle ( n = 8), 1% NaCl and aldosterone ( 0.75 mu g/h s. c., n = 8), and 1% NaCl, aldosterone, and adrenomedullin ( 1.3 mu g/kg/h s. c., n = 8). Systolic blood pressure ( SBP) and left ventricular ( LV) weight were higher in aldosterone-treated SHRs than vehicle-or vehicle/1% NaCl-treated SHRs. Thiobarbituric acid reactive substances (TBARS) levels and NADPH oxidase activity in LV tissues of aldosterone-treated SHRs were also higher than those of vehicle- or vehicle/1% NaCl-treated SHRs, and these changes were associated with increases in LV mRNA levels of p22phox, gp91phox, fibronectin, collagen types I and III, as well as collagen content. Treatment with adrenomedullin did not alter SBP or LV weight but attenuated aldosterone-induced increases in TBARS levels, NADPH oxidase activity, and mRNA levels of p22phox, gp91phox, fibronectin, collagen types I and III, as well as collagen content in LV tissues. These data suggest that NADPH oxidase-mediated reactive oxygen species production is involved in the pathogenesis of cardiac collagen accumulation in aldosterone-dependent malignant hypertensive rats and that the cardioprotective effects of adrenomedullin are mediated through the suppression of this pathway.

Web of Science ® 被引用回数 : 28

リンク情報
DOI
https://doi.org/10.1124/jpet.106.105106
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000239878900047&DestApp=WOS_CPL