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Pathophisiological study of new hypotensive peptide, adrenomedullin, using experimental medels

Research Project

Project/Area Number 06670732
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionMiyazaki Medical College

Principal Investigator

SAKATA Junichiro  Miyazaki Medical College, Research instructor, 医学部, 助手 (30253818)

Project Period (FY) 1994 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Keywordsbioactive peptide / adrenomedullin / pathophysiology / ラジオイムノアッセイ / モノクロタリン / proadorenomedullin N-terminal 20 peptide / 高血圧自然発症ラット
Research Abstract

Adrenomedullin (AM) is a new bioactive peptide recently isolated from pheochromocytoma. Summary of research results are as following.
1) Using a sensitive radioimmunoassay system for rat AM,high concentrations of immunoreactive rat AM were detected in adrenal gland, lung and cardiac atrium. In lung and atrium, the immunoreactivity concentration in rat was about 6-10 times higher than that in human. Mean plasma concentration of immunoreactive rat AM was 3.60 <plus-minus> 0.34 fmol/ml (mean <plus-minus> SD). Analysis in adrenal gland, lung and atrium with reverse phase and gel filtration high performance liquid chromatography showed that most immunoreactive rat AM emerged as a single peak at a position exactly identical to that of authentic rat AM pept
2) In order to elucidate the role of AM in hypertension, concentrations of immunoreactive rat AM and AM messenger RNA levels in tissues of spontaneously hypertensive rats (SHR) were compared with those of age-matched Wistar Kyoto rats (WKY). … More The AM immunoreactivity concentrations in adrenal gland and cardiac atrium were significantly higher in SHR than in WKY.The AM content of cardiac ventricle was also significantly higher in SHR than in WKY.The rat AM messenger RNA levels in adrenal gland and heart of SHR were also higher than those of WKY.
As for salt dependent hypertension, medel, Dahl salt-sensitive rats, the AM concentration in cardiac ventricle of the high-salt group was significantly higher than that of the low-salt group. The plasma AM concentration was also significantly higher in the high-salt group than in the low salt group. The plasma AM concentration correlated well with the weight of left ventricle. RNA blot analysis revealed that the AM mRNA level in cardiac ventricle of the high-salt group was higher than that of the low-salt group. These results suggest that AM participates in the mechanism to counteract the blood pressure elevation.
3) Proadrenomedullin N-terminal 20 peptide (PAMP) is a novel hypotensive peptide processed from an AM precursor. High concentrations of immunoreactive PAMP (ir-PAMP) were detected in rat cardiac atrium and adrenal gland by the radioimmunoassay (RIA) for rat PAMP.The mean plasma concentration of rat ir-PAMP was 3.8 <plus-minus> 0.3 fmol/ml. The ir-PAMP concentration in heart tissue of SHR was found to be increased compared with that of the control rat. The atrial concentration of ir-PAMP of SHR (5.66 <plus-minus> 0.78 fmol/mg) was significantly higher than that of the control (3.29 <plus-minus> 0.22 fmol/mg). Cardiac PAMP might have a role for the protection from systemic hyperte Less

Report

(4 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • 1994 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Junichiro Sakata,Toru Shimokubo, Kazuo Kitamura,Masatoshi Nishizono,Yoshinari Ichiki,Kenji Kangawa,Hisayuki Matsuo and Tanonao Eto.: "Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma." FEBS Lett.352. 105-108 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shin Sugo,Naoto Minamino,Kenji Kangawa,Kaoru Miyamoto,Kazuo Kitamura,Junichiro Sakata,Tanenao Eto and Hisayuki Matsuo: "Endothelial cells actively synthesize and secrete adrenomedullin." Biochem.Biophys.Res.Commun.201(3). 1160-1166 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Shimokubo,Junichiro Sakata,Kazuo Kitamura,Kenji Kangawa,Hisayuki Matsuo and Tanonao Eto: "Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats." Pathophysiology. 2. 223-226 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Shimokubo,Junichiro Sakata,Kazuo Kitamura,Kenji Kangawa,Hisayuki Matsuo and Tanonao Eto: "Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension." Life Sci.57. 1771-1779 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichirou Ishiyama,Kazuo Kitamura,Junichiro Sakata,Osamu Kida,Kenji Kangawa and Tanonao Eto: "Hemodynamic responses to rat adrenomedullin anaesthetized spontaneously hypertensive rats" Clin.Exp.Pharmacol.Physiol.22. 614-618 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haruhiko Inatsu,Junichiro Sakata,Toru Shimokubo,Michitaka Kitani,Masatoshi Nishizono,Hisanori Washimine,Kazuo Kitamura,Kenji Kangawa,Hisayuki Matsuo and Tanenao Eto: "Distribution and characterization of ratimmunoreactive proadrenomedullin N-terminal 20 peptide and the augmented cardiac pamp in spontaneously hypertensive rat." Biochem.Mol.Biol.Int.38. 365-372 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Shimokubo,Junichiro Sakata,Kazuo Kitamura,Kenji Kangawa,Hisayuki Matsuo and Tanenao Eto : Adrenomedullin: "Changes in circulating and cardiac tissue concentration in dahl salt-sensitive rats on a higy-salt diet." Clinical And Experimental Hypertension. 18(7). 949-961 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichirou Ishiyama,Kazuo Kitamura,Johji Kato,Junichiro Sakata,Kenji Kangawa and Tanonao Eto: "Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats." Hypertens.Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Junichiro Sakata, Toru Shimokubo, Kazuo Kitamura, Masatoshi Nishizono, Yoshinari Ichiki, Kenji Kangawa, Hisayuki Matsuo and Tanonao Eto: "Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma." FEBS Lett.352. 105-108 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shin Sugo, Naoto Minamino, Kenji Kangawa, Kaoru Miyamoto, Kazuo Kitamura, Junichiro Sakata, Tanenao Eto and Hisayuki Matsuo: "Endothelial cells actively synthesize and secrete adrenomedullin." Biochem.Biophys.Res.Commun.201(3). 1160-1166 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Shimokubo, Junichiro Sakata, Kazuo Kitamura, Kenji Kangawa, Hisayuki Matsuo and Tanonao Eto: "Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats." Pathophysiology. 2. 223-226 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Shimokubo, Junichiro Sakata, Kazuo Kitamura, Kenji Kangawa, Hisayuki Matsuo and Tanonao Eto: "Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension" Life Sci.57. 1771-1779 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichiro Ishiyama, Kazuo Kitamura, Junichiro Sakata, Osamu Kida, Kenji Kangawa, and Tanonao Eto: "Hemodynamic responses to rat adrenomedullin anaesthetized spontaneously hypertensive rats" Clin.Exp.Pharmacol.Physiol.22. 614-618 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Haruhiko Inatsu, Junichiro Sakata, Toru Shimokubo, Michitaka Kitani, Masatoshi Nishizono, Hisanori Washimine, Kazuo Kitamura, Kenji Kangawa, Hisayuki Matsuo and Tanenao Eto: "Distribution and characterization of rat immunoreactive proadrenomedullin N-terminal 20 peptide and the augmented cardiac pamp in spontaneously hypertensive rat." Biochem.Mol.Biol.Int.38. 365-372 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Toru Simokubo, Junichiro Sakata, Kazuo Kitamura, Kenji Kangawa, Hisayuki Matsuo and Tanenao Eto: "Adrenomedullin : Changes in circulating and cardiac tissue concentration in dahl salt-sensitive rats on a high-salt diet." Clinical And Experimental Hypertension. 18(7). 949-961 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yuichirou Ishiyama, Kazuo Kitamura, Johji Kato, Junichiro Sakata, Kenji Kangawa and Tanonao Eto: "Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats." Hypertens.Res.in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Shimokubo,T.,Sakata,J.et al: "Adrenomedullin : Changes in circulating and cardiac tissue concentration in dahl salt-sensitive rats on a high-salt diet." Clinical and Experimental Hypertension. 18. 949-961 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ishiyama,Y.,Sakata,J.et al: "Changes in cardiac adrenomedullin concentration in renovascular hypertensive rats" Hypertens.Res.in press.

    • Related Report
      1996 Annual Research Report
  • [Publications] Shimokubo,T.,Sakata,J.et al: "Alterations in tissue concentration and gene expression of adrenomedullin in spontaneously hypertensive rats." Pathophysiology. 2. 223-226

    • Related Report
      1995 Annual Research Report
  • [Publications] Shimokubo,T.,Sakata,J.et al: "Adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension." Life Sci.57. 1771-1779

    • Related Report
      1995 Annual Research Report
  • [Publications] Ishiyama,Y.,Sakata,J.et al: "Hemodynamic responses to rat adrenomedullin anaesthetized spontaneously hypertensive rats." Clin.Exp.Pharmacol.Physiol.22. 614-618

    • Related Report
      1995 Annual Research Report
  • [Publications] Junichiro Sakata: "Distribution and characterization of immunoreactive rat adrenomedullin in tissue and plasma" FEBS Letters. 352. 105-108

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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