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2005 Fiscal Year Final Research Report Summary

Elucidation of antihypertensive mechanism of small peptides and new proposal of physiological functional foods

Research Project

Project/Area Number 15380094
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Food science
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

MATSUI Toshiro  Kyushu University, Faculty of Agriculture, Associate Professor, 大学院・農学研究院, 助教授 (20238942)

Co-Investigator(Kenkyū-buntansha) MATSUMOTO Kiyoshi  KYUSHU UNIVERSITY, Professor, 大学院・農学研究院, 教授 (80038322)
KIMOTO Koichi  Tokyo Kasei University, Department of Nutritional Science, Professor, 栄養科学科, 教授 (60133378)
Project Period (FY) 2003 – 2005
KeywordsHypertension / renin-angiotensin system / peptide / Ca channel blocker / side-effect / absorption / ACE
Research Abstract

This study has focused on the elucidation of antihypertensive mechanism of bioactive small peptides on rat and cell-line experiments. Typical and new findings are as follows:
1.Di-peptide, Val-Tyr(VY) with antihypertensive ability in mild hypertensive human showed an age-dependent blood pressure lowering ; a prominent lowering effect was observed in 18-wk SHR after a single oral administration of 10 mg/kg VY, whereas less effect was obtained in 24-wk SHR.
2.As a result of peptide absorption study in 18-wk SHR, intact VY absorption was observed in the circulating blood system as well as local organ systems, in particular in the kidney and abdominal aorta the peptide was predominantly accumulated at ng/g-tissue level. Thus, it was found that VY absorbed preferably into local organs rather than blood system.
3.To clarify whether ACE inhibitoty peptides act as a bradykinin potentiator or not, correlation between peptide structure and C-/N-domain blockade of ACE was investigated. Among 65 synthetic peptides, a significant N-domain ACE inhibition was observed only for Ile-Tyr and Ile-Phe-Tyr. Knowledge on hydrophobic energy of peptides provided a useful information that peptides or compounds having the restrictive energy of 10.8 to 12.5 kJ/mol could inhibit N-domain ACE activity..
4.A potential physiological function of small peptides having ACE inhibitory activity was examined using human vascular smooth muscle cell (VSMC). As a result, VYsignificantly inhibited VSMC growth with a reduction to 59.5 % of control. In addition, inhibition of increase in 1 μM Ang II-stimulated WST-8 incorporation was observed only for VY among tested ACE inhibitory peptides. The VY-induced inhibition was not affected in the presence of AT_1 receptor antagonist (1 μM of losartan) at all. Finally, VY inhibited a Bay K 8644-stimulated VSMC proliferation, indicating that VY with ACE inhibitory activity also acts as an L-type Ca2+ channel blocker.

  • Research Products

    (10 results)

All 2005 2004

All Journal Article (10 results)

  • [Journal Article] Determination of Antihypertensive Small Peptides, Val-Tyr, by Fluorimetric High-performance Liquid Chromatography Combined with a Double Heart-Cut Column-Switching Technique2005

    • Author(s)
      T.Ueno
    • Journal Title

      Analytical Science 21・8

      Pages: 997-1000

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Antiproliferative action of an angiotensin I-converting enzyme inhibitory peptide, Val-Tyr, via an L-type Ca^<2+> channel inhibition in cultured vascular smooth muscle cells.2005

    • Author(s)
      T.Matsui
    • Journal Title

      Hypertension Research 28・6

      Pages: 545-552

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Determination of Antihypertensive Small Peptides, Val-Tyr and Ile-Val-Tyr, by Fluorimetric High-Performance Liquid Chromatography Combined with a Double Heart-Cut Column-Switching Technique.2005

    • Author(s)
      T.Ueno
    • Journal Title

      Analytical Science 21-8

      Pages: 997-1000

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Antiproliferative action of an angiotensin I-converting enzyme inhibitory peptide, Val-Tyr, via an L-type Ca^<2+> channel inhibition in cultured vascular smooth muscle cells.2005

    • Author(s)
      T.Matsui
    • Journal Title

      Hypertension Research 28-6

      Pages: 545-552

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats2004

    • Author(s)
      T.Matsui
    • Journal Title

      Journal of Peptide Science 10

      Pages: 535-545

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] ACE inhibitory peptides can act as an inhibitor of vascular smooth muscle cell growth2004

    • Author(s)
      H.Oka
    • Journal Title

      Journal of Human Hypertension 22・S1

      Pages: S68

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Classification of natural ACE inhibitory peptides into C-/N-domain selective inhibitor2004

    • Author(s)
      T.Matsui
    • Journal Title

      Journal of Human Hypertension 22・S1

      Pages: S70

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Tissue distribution of antihypertensive dipeptide, Val-Tyr, after its single oral administration to spontaneously hypertensive rats.2004

    • Author(s)
      T.Matsui
    • Journal Title

      Journal of Peptide Science 10

      Pages: 535-545

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] ACE inhibitory peptides can act as an inhibitor of vascular smooth muscle cell growth.2004

    • Author(s)
      H.Oka
    • Journal Title

      Journal of Human Hypertension 22-S1

      Pages: S68

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Classification of natural ACE inhibitory peptides into C-/N-domain selective inhibitor.2004

    • Author(s)
      T.Matsui
    • Journal Title

      Journal of Human Hypertension 22-S1

      Pages: S70

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2007-12-13  

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