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1998 Fiscal Year Final Research Report Summary

Effects of Docosahexaenoic Acids on Vascular Cell Functions

Research Project

Project/Area Number 09672244
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionHealth Sciences University of Hokkaido

Principal Investigator

HIRAFUJI Masahiko  Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 薬学部, 助教授 (20142987)

Co-Investigator(Kenkyū-buntansha) HAMAUE Naoya  Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Instr, 薬学部, 助手 (70221504)
Project Period (FY) 1997 – 1998
Keywordsdocosahexaenoic acid / vascular smooth muscle cells / intracellular calcium / nitric oxide / calcium channels / 5-hydroxytryptamine / angiotensin II
Research Abstract

The aim of the present project was to investigate the effects of docosahexaenoic acids (DHA) on vascular cells functions, using cultured aortic smooth muscle cells. Treatment of rat aortic smooth muscle cells with DHA in culture had no significant effect on the cell growth rate and cell hypertrophy induced by angiotensin II.The effects of DHA on intracellular C^<2+> dynamics and nitric oxide (NO) production were also examined using cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). The resting and peak concentrations of intracellular C^<2+> were significantly higher in cells from SHRSP than in WKY stimulated with angiotensin II or 5-hydroxytryptamine (5-HT). DHA treatment significantly suppressed the intracellular C^<2+> dynamics induced by angiotensin II and 5-HT in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. It was suggested that DHA inhibited C^<2+> influx through the voltage-dependent o … More r 2nd messenger-operated C^<2+> channels, but not store-operated channels. The total NO production induced by interleukin-1beta (IL-1beta) was significantly lower in cells from SHRSP than from WKY.DI-LA treatment significantly increased IL-l3b-induced NO production in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. The increase in NO production was due to the stimulation of inducible NO synthase protein induction, as analyzed by Western bloffing method. It is also suggested that DHA treatment can prevent cell damage evoked by IL-lbeta-induced NO.These studies suggest that the altered intracellular C^<2+> dynamics induced by contractile agonists and the diminished NO production in vascular smooth muscle cells play a role in the pathophysiology of SHRSP.Since the intracellular Ca and NO plays an important role in vascular smooth muscle cell functions, the properties to improve these functions can be contributed to the beneficial effect of DHA on cardiovascular disorders. Less

  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Hirafuji, M.: "Autihyperteusive wechavisws of docosahexaeueic acid(DHA)-Influences on vascular smooth muscle cells in culture" Jap.Heart J.38(4). 568 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 平藤雅彦: "血管平滑筋細胞機能に対するドコサヘキサエン酸の特異的調節作用" 日本薬理学雑誌. 110(補1). 171-176 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M.: "Suppressive effect of serotarin on nitrix oxide production by vascular smooth muscle cells isolated from strok prove spoataneousluy hyperteusive rats" Jap.Heart J.39(4). 560 (19987)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M.: "Effect of docosahexaenoic acid on smooth muscle cell functions" Life Sci.62. 1689-1693 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, J.: "Effect of 5-hydroxytryptamine on intracellular calcium dynamics in cultured rat vascular smooth muscle cells" Res.Comm.Mol.Pathol.Pharwacol.99(3). 305-319 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M.: "Effect of docosahexaenoic acid on intracellular colcium dynamics in vascular smooth muscle cell from normotensive and geretically hypertersive rats" Res.Comm.Mol.Pathol.Pharmacd.102(1). 29-42 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M.: "The Biology of Nitric Oxide" Portland Press, UK, 350 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M.: "Genetical, Immune and Molecular Disposition to Hypertension" VSP International Press, Zeist, The Nether lands (in press), (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hirafuji, M., Ebihara, T., Kawahara, F., Kanai, Y., Kato, K., Tanimura, A., Saito, H.and Minami, M.: "Antihypertensive mechanisms of docosahexaenoic acid(DHA)-Influences on vascular smooth muscle cells in culture." Jpn.Heart J. 38(4). 568 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Ebihara, T., Kawahara, F., Tsunoda, M., Hamaue, N., Tanimura, A.and Minami, M.: "Specific modulation of vascular smooth muscle cell functions by docosahexaenoic acid(DHA)" Folia Pharmacol.Jpn.110, Suppl1. 171-176 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Kanai, Y., Tsunoda, M., Ebihara, T., Kawahara, F.and Minami, M.: "Suppressive effect of serotonin on nitric oxide production by vascular smooth muscle cells isolated from stroke-prone spontaneously hypertensive rats." Jpn.Heart J. 39(4). 560 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Ebihara, T., Kawahara, F.and Minami, M.: "Effect of docosahexaenoic acid on smooth muscle cell functions." Life Sci.62. 1689-1693 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Nezu, A., Kanai, Y., Ebihara, T., Kawahara, F., Tanimura, A.and Minami, M.: "Effect of 5-hydroxytryptamine on intracellular calcium dynamics in cultured rat vascular smooth muscle cells." Res.Commun.Mol.Pathol.Pharmacol.99(3). 305-319 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Ebihara, T., Kawahara, F., Nezu, A., Tanimura, A., H.Saito and Minami, M.: "Effect of docosahexaenoic acid on intracellular calcium dynamics in vascular smooth muscle cells from normotensive and genetically hypertensive rats." Res.Commun.Mol.Pathol.Pharmacol.102(1). 29-42 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Kanai, Y., Tsunoda, M., Ebihara, T., Kawahara, F.and Minami, M.: Nitric Oxide Production by Vascular Smooth Muscle Cells From Stroke-prone Spontaneously Hypertensive Rats, In, The Biology of Nitric Oxide, Part 6. Ed.by Moncada, S., Toda, N., Maeda, H.and Higgs, E.A., Portland Press, London and Minami, 153 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hirafuji, M., Minami, M., Ebihara, T., Kawahara, F., Yoshioka, M., Saito, H.and Parvez, H.S.: Changes in intracellular Ca2+ signaling induced by docosahexaenoic acid in vascular smooth muscle cells from a genetical hypertensive rat(SHRSP), In Progress in Hypertension, Vol.4. Ed.by Parvez, S.H., Frossard, P.M., Minami, M., Parvez, S.and Saito, H., VSP BV,Utrecht, The Netherlands(in press), (1999)

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      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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