Adrenomedullin Infusion Attenuates Myocardial Ischemia/Reperfusion Injury Through the Phosphatidylinositol 3-Kinase/Akt-Dependent Pathway

DOI Web Site 被引用文献9件
  • Hiroyuki Okumura
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Noritoshi Nagaya
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Takefumi Itoh
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Ichiro Okano
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Jun Hino
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Kenji Mori
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Yoshitane Tsukamoto
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Hatsue Ishibashi-Ueda
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Senri Miwa
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Keiichi Tambara
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Shinya Toyokuni
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Chikao Yutani
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.
  • Kenji Kangawa
    From the Department of Biochemistry (H.O., I.O., J.H., K.M., K.K.), National Cardiovascular Center Research Institute, Osaka, Japan; Department of Internal Medicine (N.N., T.I.) and Department of Pathology (Y.T., H.I.-U., C.Y.), National Cardiovascular Center, Osaka, Japan; and Department of Cardiovascular Surgery (S.M., K.T.) and Department of Pathology and Biology of Diseases (S.T.), Graduate School of Medicine, Kyoto University, Kyoto, Japan.

説明

<jats:p> <jats:bold> <jats:italic>Background—</jats:italic> </jats:bold> Infusion of adrenomedullin (AM) has beneficial hemodynamic effects in patients with heart failure. However, the effect of AM on myocardial ischemia/reperfusion remains unknown. </jats:p> <jats:p> <jats:bold> <jats:italic>Methods and Results—</jats:italic> </jats:bold> Male Sprague-Dawley rats were exposed to a 30-minute period of ischemia induced by ligation of the left coronary artery. They were randomized to receive AM, AM plus wortmannin (a phosphatidylinositol 3-kinase [PI3K] inhibitor), or saline for 60 minutes after coronary ligation. Hemodynamics and infarct size were examined 24 hours after reperfusion. Myocardial apoptosis was also examined 6 hours after reperfusion. The effect of AM on Akt phosphorylation in cardiac tissues was examined by Western blotting. Intravenous administration of AM significantly reduced myocardial infarct size (28±4% to 16±1%, <jats:italic>P</jats:italic> <0.01), left ventricular end-diastolic pressure (19±2 to 8±2 mm Hg, <jats:italic>P</jats:italic> <0.05), and myocardial apoptotic death (19±2% to 9±4%, <jats:italic>P</jats:italic> <0.05). Western blot analysis showed that AM infusion accelerated Akt phosphorylation in cardiac tissues and that pretreatment with wortmannin significantly attenuated AM-induced Akt phosphorylation. Moreover, pretreatment with wortmannin abolished the beneficial effects of AM: a reduction of infarct size, a decrease in left ventricular end-diastolic pressure, and inhibition of myocardial apoptosis after ischemia/reperfusion. </jats:p> <jats:p> <jats:bold> <jats:italic>Conclusions—</jats:italic> </jats:bold> Short-term infusion of AM significantly attenuated myocardial ischemia/reperfusion injury. These cardioprotective effects are attributed mainly to antiapoptotic effects of AM via a PI3K/Akt-dependent pathway. </jats:p>

収録刊行物

  • Circulation

    Circulation 109 (2), 242-248, 2004-01-20

    Ovid Technologies (Wolters Kluwer Health)

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