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Molecular Pharmacological Studies on Effect of Docosahexaenoic Acid on Vascular Cell Functions

Research Project

Project/Area Number 11672177
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 Associate Professor, 薬学部, 助教授 (20142987)

Co-Investigator(Kenkyū-buntansha) HAMAUE Naoya  Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Instructor, 薬学部, 助手 (70221504)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordsdocosahexaenoic acid / eicosapentaenoic acid / vascular smooth muscle cells / nitric oxide / iNOS / prostaglandin I2 / cyclooxygenase / 一酸化窒素合成酵素 / シクロオキシゲナーゼ-2 / 遺伝子発現 / ラット / 血管内皮細胞 / 高血圧
Research Abstract

The aim of the present project was to investigate the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), n-3 polyunsaturated fatty acids, on protein and mRNA expressions of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in cultured vascular smooth muscle cells isolated from 6-7 week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched normotensive Wistar Kyoto rats (WKY). The IL-1β-induced nitric oxide (NO) production and iNOS expression in cells of SHRSP were significantly lower than those in cells of WKY.Similarly, prostaglandins (PG)I2 production and COX-2 expression were significantly lower in cells of SHRSP than WKY, whereas there was no difference in the COX-1 expression. There were no significant differences in iNOS and COX-2 mRNA expressions between the two strains, suggesting that these protein expression may be impaired at post-transcriptional process in cells of SHRSP.DHA and EPA significantly enhanced the IL-1β-induced NO production in a concentration-dependent manner in cells of WKY, whereas had no effect in cells of SHRSP.DHA and EPA also significantly enhanced iNOS protein and mRNA expressions induced by IL-1β in cells of WKY but not in cells of SHRSP.DHA and EPA significantly increased COX-2, but not COX-1, protein expression induced by IL-1β in cells of WKY, but had no effect on COX-2 mRNA expression. These results suggest that the impairment of iNOS and COX-2 expressions in vascular smooth muscle cells may have relevance to the pathophysiology in SHRSP.These results further suggest that enhancement of NO and PGI2 productions by DHA may account for its beneficial effect on cardiovascular disorders.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Hirafuji,M.: "5-Hydroxytryptamine, lutnotangiotensin II, induces transient…"Europ.J.Pharmacol.. 380. 163-170 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平藤雅彦: "腸クロム親和性細胞の細胞内カルシウム動態解析法"日本薬理学雑誌. 114. 357-363 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji,M.: "Effect of daosahexaenoic acid on nitric oxide production…"Clin.Exp.Hypertens.. 22(4). 349-350 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji,M.: "Intracellular regulatory mechanisms of 5-HT release…"Biogenic Amines. 16(1). 29-52 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平藤雅彦: "ドコサヘキサエン酸はなぜ循環器疾患に有効なのか-血管…"道薬誌. 18(1). 30-35 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 平藤雅彦: "正常および高血圧ラット由来血管平滑筋細胞のNO/iNOS…"血管. 24(2). 37-42 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji,M.: "Progress in Hypertension, Vol.4"Parveg,SH, Frossard, PM, Minami M, Parveg S and Sato H. 267 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Minami, M., Ebihara, T., Kawahara, F., Yoshioka, M., Saito, H.and Parvez, H.S.: "Changes in intracellular Ca^<2+> signaling induced by docosahexaenoic acid in vascular smooth muscle cells from a genetical hypertensive rats (SHRSP)"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. 157-173 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Kawahara, F., Ebihara, T., Nezu, A., Tanimura, A.and Minami, M.: "5-Hydroxytryptamine, but not angiotensin II, induces transient Ca^<2+> influx through Ni^<2+>-insensitive Ca^<2+> channel in rat vascular smooth muscle cells"Eur.J.Pharmacol.. 380. 163-170 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Satoh, Y.and Minami, M.: "Analysis of intracellular calcium dynamics in enterochromaffin cells of small intestine"Folia Pharmacol.Jpn.. 114. 357-363 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Hamaue, N., Endo, T.and Minami, M.: "Effect of docosahexaenoic acid on nitric oxide production by vascular smooth muscle cells isolated from WKY and SHRSP"Clin.Exp.Hypertens.. 22 (4). 349-350 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Minami, M., Endo, T., Ogawa, T., Kato, K., Yoshioka, M.and Parvez, S.H.: "Intracellular regulatory mechanisms of 5-HT release from enterochromaffin cells in intestinal mucosa."Biogenic Amines. 16 (1). 29-52 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M.: "Why docosahexaenoic acid is effective for cardiovascular disorders? -relevance to vascular smooth muscle cell functions."J.Hokkaido Pharmaceut.Assoc.. 18 (1). 30-35 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji, M., Machida, T., Kawahara, A.and Minami, M.: "NO production and iNOS expression by vascular smooth muscle cells of normotensive and genetically hypertensive rats : effect of docosahexaenoic acid (DHA)."Jpn.J.Circ.Res.. 24 (2). 37-42 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hirafuji,M.: "Effect of docosahexaenoic acid on nitric oxide production by vascular smooth muscle cells isolated from WKY and SHRSP"Clinical and Experimental Hypertension. 22(4). 349-350 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hirafuji,M.: "Intraellular regulatory mechanisms of 5-HT release from enterochromaffin cells in intestinal mucosa"Biogenic Amines. 16(1). 29-52 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 平藤雅彦: "ドコサヘキサエン酸はなぜ循環器疾患に有効なのか-血管平滑筋細胞機能との関連"北海道薬剤師会雑誌. 18(1). 30-35 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Hirafuji: "5-Hydorxytryptawine iuduces trausient Ca^<2+> influx through Ni^<2+>-insensitive Ca^<2+> channels in rat vaswlar smooth muscle cells"European Journal of Pharwacology. 380. 163-170 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 平藤雅彦: "腸クロム親和性細胞の細胞内カルシウム動態解析法"日本薬理学雑誌. 114(12). 357-363 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Hirafuji: "Progress in hypertension,Vol.4"S.H.Parrez、P.M.Frossard、M.Minami,S.Parvez and H.Saito. 266 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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