Direct evidence for increased hydroxyl radicals originating from superoxide in the failing myocardium

Tomomi Ide, Hiroyuki Tsutsui, Shintaro Kinugawa, Nobuhiro Suematsu, Shunji Hayashidani, Kazuhiro Ichikawa, Hideo Utsumi, Youji Machida, Kensuke Egashira, Akira Takeshita

研究成果: ジャーナルへの寄稿学術誌査読

346 被引用数 (Scopus)

抄録

Experimental and clinical studies have suggested an increased production of reactive oxygen species (ROS) in the failing myocardium. The present study aimed to obtain direct evidence for increased ROS and to determine the contribution of superoxide anion (·O2-), H2O2, and hydroxy radical (·OH) in failing myocardial tissue. Heart failure was produced in adult mongrel dogs by rapid ventricular pacing at 240 bpm for 4 weeks. To assess the production of ROS directly, freeze-clamped myocardial tissue homogenates were reacted with the nitroxide radical, 4-hydroxy-2,2,6,6,-tetramethyl- piperidine-N-oxyl, and its spin signals were detected by electron spin resonance spectroscopy. The rate of electron spin resonance signal decay, proportional to ·OH level, was significantly increased in heart failure, which was inhibited by the addition of dimethylthiourea (·OH scavenger) into the reaction mixture. Increased ·OH in the failing heart was abolished to the same extent in the presence of desferrioxamine (iron chelator), catalase (H2O2 scavenger), and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron; LaMotte) (·O2- scavenger), indicating that ·OH originated from H2O2 and ·O2-. Further, ·O2- produced in normal myocardium in the presence of antimycin A (mitochondrial complex III inhibitor) could reproduce the increase of H2O2 and ·OH seen in the failing tissue. There was a significant positive relation between myocardial ROS level and left ventricular contractile dysfunction. In conclusion, in the failing myocardium, ·OH was produced as a reactive product of ·O2- and H2O2, which might play an important role in left ventricular failure.

本文言語英語
ページ(範囲)152-157
ページ数6
ジャーナルCirculation research
86
2
DOI
出版ステータス出版済み - 2000

!!!All Science Journal Classification (ASJC) codes

  • 生理学
  • 循環器および心血管医学

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