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Research for the role of endothelium-dependent relaxation in the change of maternal circulation during pregnancy

Research Project

Project/Area Number 13671700
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

SAKAMOTO Shuichi  Tokyo Medical and Dental University, Graduate school, lecturer (90242198)

Co-Investigator(Kenkyū-buntansha) ASO Takeshi  Tokyo Medical and Dental University, Graduate school, Professor (60093176)
AZUMA Hiroshii  Tokyo Medical and Dental University, Professor (20134736)
KUBOTA Toshiro  Tokyo Medical and Dental University, Graduate school, Associate Professor (50126223)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
KeywordsHind-limb perfusion model / CCh-induced relaxation / EDHF / K^+ ion / metabolite(s) of P_<450> mono-oxygenase / ラット下肢潅流モデル / ラットの下肢潅流モデル / 内皮依存性脱分極因子(EDHF) / K^+ / 妊娠 / 末梢血管抵抗 / 下肢還流モデル / H_2O_2 / 末梢血管 / 一酸化窒素(NO) / 内皮依存性過分極因子(EDHF)
Research Abstract

We examined the involvement of NO and/or EDHF in decreasing peripheral vascular resistance in hind limb perfusion model of the rat, and analyzed the identity of EDHF in this model. The potency of carbachol (CCh) to produce relaxation was quantitatively similar to sodium nitroprusside (SNP). CCh-induced relaxation was abolished after endothelial denudation, but resistant to nitroarginine and indomethacin. The relaxation was inhibited by tetraethylammonium, ouabain, charybdotoxin plus apamin and under depolarization. SNP-induced relaxation was accompanied by the increased cGMP production, which was inhibited by ODQ. Although carbachol produced similar extent of relaxation to SNP, cGMP level was 24 times lower than that with SNP. Low KCI produced a definite relaxation, which was inhibited by ouabain, but independent of NO, prostacyclin and endothelium. 1-EBIO as an activator of IK_<Ca> channel also produced a concentration-dependent relaxation, which was inhibited by charybdotoxin, ouabai … More n and depolarization, but independent of NO and prostacyclin. Clotrimazole and 17-octadecynoic acid as inhibitors of P_<450> mono-oxygenase inhibited the carbachol-induced relaxation. Meanwhile, catalase at a concentration sufficient to inhibit H_2O_2- induced relaxation did not exert definite inhibition of the carbachol-induced relaxation. These results suggest that carbachol produces an endothelium-dependent, EDHF-dependent and NO-cGMP independent relaxation and that K^+ and metabolite(s) of P_<450> mono-oxygenase possibly play an important role for this relaxation. We also we investigated whether the responsiveness of peripheral resistant vessels of the hind limb changes during pregnancy, and the contribution of NO and EDHF to these changes was pharmacologically analyzed using a hind-limb perfusion model of the rat. In the end stage of pregnancy, peripheral vascular resistance was decreased in our model. The enhanced decrease in the peripheral vascular resistance, which is mediated by EDHF and partly due to the increased sensitivity of the pathway downstream the cGMP generation, possibly results in lowering the blood pressure and hyporesposiveness to vasoconstrictors at the term gestation of the rat. Less

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (4 results)

All 2002 Other

All Journal Article (2 results) Publications (2 results)

  • [Journal Article] Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat.2002

    • Author(s)
      R.Loyaga, S.Sakamoto, T.Aso, Y.Yamauchi, H.Azuma
    • Journal Title

      Proceedings of 54^th Annual Congress of the Japan Society of Obstetrics and Gynecology

      Pages: 39-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat2002

    • Author(s)
      R.Loyaga, S.Sakamoto, T.Aso, Y.Yamauchi, H.Azuma
    • Journal Title

      Proceedings of 54^<th> Annual Congress of the Japan Society of Obstetrics and Gynecology

      Pages: 39-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] R.Loyaga, S.Sakamoto, et al.: "EDHF in the vasodilation of the peripheral resistant vessels of the rat"Journal of Pharmacological Sciences. 94 suppl 1. (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] R.Loyaga, S.Sakamoto, T.Aso, Y.Yamauchi, H.Azuma: "Changes in the responsiveness of peripheral resistant vessels during pregnancy of the rat"Proceeding of 54th annual congress of the Japan society of obstetrics and gynecology. 39-44 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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