Role of Endogenous Adrenomedullin in the Regulation of Vascular Tone and Ischemic Renal Injury

DOI Web Site 被引用文献21件
  • Hiroaki Nishimatsu
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Yasunobu Hirata
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Takayuki Shindo
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Hiroki Kurihara
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Masao Kakoki
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Daisuke Nagata
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Hiroshi Hayakawa
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Hiroshi Satonaka
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Masataka Sata
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Akihiro Tojo
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Etsu Suzuki
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Kenji Kangawa
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Hisayuki Matsuo
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Tadaichi Kitamura
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.
  • Ryozo Nagai
    From the Departments of Urology (H.N., T.K.) and Internal Medicine (Y.H., T.S., H.K., M.K., D.N., H.H., H.S., M.S., A.T., E.S., R.N.), Faculty of Medicine, The University of Tokyo; and the Research Institute (K.K., H.M.), National Center of Cardiovascular Medicine, Japan.

書誌事項

タイトル別名
  • Studies on Transgenic/Knockout Mice of Adrenomedullin Gene

抄録

<jats:p> Adrenomedullin (AM) is a potent depressor peptide whose vascular action is suggested to involve nitric oxide (NO) release. To explore the role of endogenous AM in vascular and renal function, we examined the effects of acetylcholine (ACh), AM, and AM receptor antagonists AM(22-52) and CGRP(8-37) on the renal perfusion pressure (RPP) of kidneys isolated from AM transgenic (TG)/heterozygote knockout (KO) mice and wild-type littermates (WT). Furthermore, we evaluated the renal function and histology 24 hours after bilateral renal artery clamp for 45 minutes in TG, KO, and WT mice. Baseline RPP was significantly lower in TG than in KO and WT mice (KO 93.4±4.6, WT 85.8±4.2, TG 72.4±2.4 mm Hg [mean±SE], <jats:italic>P</jats:italic> <0.01). ACh and AM caused a dose-related reduction in RPP, but the degree of vasodilatation was smaller in TG than that in KO and WT (%ΔRPP 10 <jats:sup>−7</jats:sup> mol/L ACh: KO −48.1±3.9%, WT −57.5±5.6%, TG −22.8±4.8%, <jats:italic>P</jats:italic> <0.01), whereas <jats:italic>N</jats:italic> <jats:sup>G</jats:sup> -nitro- <jats:sc>l</jats:sc> -arginine methyl ester (L-NAME) caused greater vasoconstriction in TG (%ΔRPP 10 <jats:sup>−4</jats:sup> mol/L: KO 33.1±3.3%, WT 55.5±7.2%, TG 152.6±21.2%, <jats:italic>P</jats:italic> <0.01). Both AM antagonists increased RPP in TG to a greater extent compared with KO and WT mice (%ΔRPP 10 <jats:sup>−6</jats:sup> mol/L CGRP(8-37): KO 12.8±2.6%, WT 19.4±3.6%, TG 41.8±8.7%, <jats:italic>P</jats:italic> <0.01). In mice with ischemic kidneys, serum levels of urea nitrogen and renal damage scores showed smaller values in TG and greater values in KO mice (urea nitrogen: KO 104±5>WT 98±15>TG 38±7 mg/dL, <jats:italic>P</jats:italic> <0.05 each). Renal NO synthase activity was also greater in TG mice. However, the differences in serum urea nitrogen and renal damage scores among the 3 groups of mice were not observed in mice pretreated with L-NAME. In conclusion, AM antagonists increased renal vascular tone in WT as well as in TG, suggesting that endogenous AM plays a role in the physiological regulation of the vascular tone. AM is likely to protect renal tissues from ischemia/reperfusion injury through its NO releasing activity. </jats:p>

収録刊行物

  • Circulation Research

    Circulation Research 90 (6), 657-663, 2002-04-05

    Ovid Technologies (Wolters Kluwer Health)

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