Renoprotective Effect of Chronic Adrenomedullin Infusion in Dahl Salt-Sensitive Rats

DOI Web Site 被引用文献8件
  • Toshio Nishikimi
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Yosuke Mori
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Naohiko Kobayashi
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Kazuyoshi Tadokoro
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Xin Wang
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Kazumi Akimoto
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Fumiki Yoshihara
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Kenji Kangawa
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.
  • Hiroaki Matsuoka
    From the Department of Hypertension and Cardiorenal Medicine (T.N., Y.M., N.K., K.T., X.W., H.M.), and Laboratory of Molecular and Cellular Biology (K.A.), Dokkyo University School of Medicine, Tochigi; and Research Institute National Cardiovascular Center (F.Y., K.K.), Osaka, Japan.

抄録

<jats:p>The present study was designed to examine whether chronic adrenomedullin infusion has renoprotective effects in hypertensive renal failure and the mechanism by which chronic adrenomedullin infusion exerts its effects. Dahl salt-sensitive rats and Dahl salt-resistant rats were fed a high salt diet starting at 6 weeks of age. Recombinant human adrenomedullin or vehicle was infused for 7 weeks in 11-week-old Dahl salt-sensitive rats. Dahl salt-resistant rat was used as a control. After 7 weeks, untreated Dahl salt-sensitive rats were characterized by decreased kidney function, abnormal morphological findings, increased hormone levels, increased renal tissue angiotensin II levels, and altered mRNA expressions of transforming growth factor β (TGF-β) and components of the renin-angiotensin system compared with Dahl salt-resistant rats. Chronic adrenomedullin treatment significantly improved renal function (serum creatinine −87%, creatinine clearance +114%, urinary protein excretion −59%) and histological findings (glomerular injury score −54%) without changing mean arterial pressure compared with untreated Dahl salt-sensitive rats. Interestingly, long-term human adrenomedullin infusion decreased the endogenous rat adrenomedullin level (−97%) with a slight increase of human adrenomedullin level. Chronic adrenomedullin treatment also significantly inhibited the increase of plasma renin concentration (−269%), aldosterone level (−82%), and renal tissue angiotensin II levels (−60%). Furthermore, adrenomedullin infusion significantly decreased the increases of mRNA expressions of TGF-β (− 63%), angiotensin-converting enzyme (−137%), renin (−230%), and angiotensinogen (−38%) in renal cortex. These results suggest that increased endogenous adrenomedullin plays a compensatory role in chronic hypertensive renal failure and that long-term adrenomedullin infusion has renoprotective effects in this type of hypertension model, partly via inhibition of the circulating and renal renin-angiotensin system.</jats:p>

収録刊行物

  • Hypertension

    Hypertension 39 (6), 1077-1082, 2002-06

    Ovid Technologies (Wolters Kluwer Health)

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