Mitochondria-Derived Reactive Oxygen Species and Vascular MAP Kinases

DOI Web Site 被引用文献6件
  • Shoji Kimura
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Guo-Xing Zhang
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Akira Nishiyama
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Takatomi Shokoji
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Li Yao
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Yu-Yan Fan
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Matlubur Rahman
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.
  • Youichi Abe
    From the Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.

書誌事項

タイトル別名
  • Comparison of Angiotensin II and Diazoxide

抄録

<jats:p> Reactive oxygen species (ROS) are key mediators in signal transduction of angiotensin II (Ang II). However, roles of vascular mitochondria, a major intracellular ROS source, in response to Ang II stimuli have not been elucidated. This study aimed to examine the involvement of mitochondria-derived ROS in the signaling pathway and the vasoconstrictor mechanism of Ang II. Using 5-hydroxydecanoate (5-HD; a specific inhibitor of mitochondrial ATP-sensitive potassium [mitoK <jats:sub>ATP</jats:sub> ] channels) and tempol (a superoxide dismutase mimetic), the effects of Ang II and diazoxide (a mitoK <jats:sub>ATP</jats:sub> channel opener) were compared on redox-sensitive mitogen-activated protein (MAP) kinase activation in rat vascular smooth muscle cells (RVSMCs) in vitro and in rat aorta in vivo. Stimulation of RVSMCs by Ang II or diazoxide increased phosphorylated MAP kinases (ERK1/2, p38, and JNK), as well as superoxide production, which were then suppressed by 5-HD pretreatment in a dose-dependent manner, except for ERK1/2 activation by Ang II. The same events were reproduced in rat aorta in vivo. Ang II-like diazoxide depolarized the mitochondrial membrane potential (ΔΨ <jats:sub>M</jats:sub> ) of RVSMCs determined by JC-1 fluorescence, which was inhibited by 5-HD. 5-HD did not modulate Ang II–induced calcium mobilization in RVSMCs and did not affect on the vasoconstrictor effect in either acute or chronic phases of Ang II–induced hypertension. These results reveal that Ang II stimulates mitochondrial ROS production through the opening of mitoK <jats:sub>ATP</jats:sub> channels in the vasculature-like diazoxide, leading to reduction of ΔΨ <jats:sub>M</jats:sub> and redox-sensitive activation of MAP kinase; however, generated ROS from mitochondria do not contribute to Ang II–induced vasoconstriction. </jats:p>

収録刊行物

  • Hypertension

    Hypertension 45 (3), 438-444, 2005-03

    Ovid Technologies (Wolters Kluwer Health)

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