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Biochemical and Molecular Biological Investigation of the Pregnancy Associated Uterine Blood Flow Increase-As a Basic Study for Developing Future Treatment of Intrauterine Growth Retardation-

Research Project

Project/Area Number 11671611
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

ITOH Hiroaki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (70263085)

Co-Investigator(Kenkyū-buntansha) FUJII Shingo  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (30135579)
MANDAI Masaki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助手 (80283597)
SAGAWA Norimasa  Kyoto University, Graduate School of Medicine, Associate Professor, 医学研究科, 助教授 (00162321)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordspregnancy / uterine artery / nitric oxide / cGMP / CNP / Nitric Oxide / nitric oxide(NO) / prostacyclin / estorgen receptor
Research Abstract

Pregnancy increases uterine artery blood flow approximately 30 fold for supply oxygen and nutrition to developing fetus, the physiological mechanism of which has not been fully clarified. Recently, pulsed Doppler ultrasound investigations suggested a possibility that this physiological increase of uterine blood flow was disturbed in some cases of intrauterine growth retardation (IUGR). Therefore, the aim of the study is to investigate, the possible involvement of two major guanylate cyclase systems, nitric oxide (NO) / soluble gaunylate system (sGC) andC-type natriuretic peptide (CNP) / particulate guanylate cyclase-B (GC-B) system, in the regulation of uterine artery blood flow during pregnancy.
In this study we revealed that pregnancy increased the protein and mRNA expression of endothelial NO synthase (eNOS), sGC, CNP and GC-B increased in uterine artery, but not renal nor omental arteries from pregnant sheep. The in vitro enzyme activities of both sGC and GC-B, estimated by cGMP pro … More duction, in the tissues of uterine arteries from pregnant sheep was significantly higher than those renal or omental arteries. This local up-regulation of cGMP generation in uterine artery was not observed in nonpregnant sheep. Thus, both NO/sGC and CNP/GC-B pathways were specifically up-regulated in ovine uterine artery during pregnancy, contributing to uterine artery blood flow increase by augmenting local cGMP generation.
Moreover, the plasma cGMP concentrations in normal pregnant women were significantly elevated during pregnancy, which suggested a possibility that the up-regulation of guanylate cyclate system might be also involved in human uterine artery blood flow increase during pregnancy. The plasma cGMP concentrations in mild preeclampsia pregnant women were significantly higher than those in severe preeclampsia, for all maternal severe hyper tension as well as complication with IUGR.These data all together suggested an interesting possibility that the preganacy associated up-regulation of systemic and/or local guanylate cyclase system might be deteriorated in cases of maternal severe preeclampsia. Less

Report

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

    (24 results)

All Other

All Publications (24 results)

  • [Publications] H Itoh, 他6名: "Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy, a review."Trophoblast Research. 13. 301-309 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H Itoh, 他4名: "Basic fibroblast growth factor decrease clearance receptor of natriuretic pepteide feto-placental artery endothelium."Am J Physiol. 46. R541-R547 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N Sagawa,H Itoh, 他11名: "Leptin is a novel placenta-derived hormone in humans."Taiwanese J Obstet Gynecol. 38. 1-10 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N Sagawa,H Itoh, 他11名: "leptin as a novel placenta-derived hormone in humans."Trophoblast Research. 13. 25-34 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KK Okumura,H Itoh, 他6名: "Platelet activating factor-acetylhydrolase activity and nitric oxide metabolite level in plasma of pregnant women who developed transient hypertension later during pregnancy."Reprod Fertil Dev. 11. 75-79 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S Yura,H Itoh, 他7名: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-755 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H Itoh, et al.: "Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy, a review"Trophoblast Research. 13. 301-309 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H Itoh, et al.: "Basic fibroblast growth factor decrease clearance receptor of natriuretic pepteide feto-placental artery endothelium."Am J Physiol. 46. R541-R547 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N Sagawa, H Itoh, et al.: "Leptin is a novel placenta-derived hormone in humans."Taiwanese J Obstet Gynecol. 38. 1-10 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] N Sagawa, H Itoh, et al.: "leptin as a novel placenta-derived hormone in humans."Trophoblast Research. 13. 25-34 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] KK Okumura, H Itoh, et al.: "Platelet activating factoracetylhydrolase activity and nitric oxide metabolite level in plasma of pregnant women who developed transient hypertension later during pregnancy."Reprod Fertil Dev. 11. 75-79 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] S Yura, H Itoh, et al.: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-755 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] H Itoh 他6名: "Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy, a review."Trophoblast Research. 13. 301-309 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] H Iton 他4名: "Basic fibroblast growth factor decrease clearance receptor of natriuretic pepteide feto-placental artery endothelium."Am J Physiol. 46. R541-R547 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] N Sagawa,H Itoh 他11名: "Leptin is a novel placenta-derived hormone in humans."Taiwanese J Obstet Gynecol. 38. 1-10 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] N Sagawa,H Itoh 他11名: "leptin as a novel placenta-derived hormone in humans."Trophoblast Research. 13. 25-34 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] KK Okumura,H Itoh 他6名: "Platelet activating factor-acetylhydrolase activity and nitric oxide metabolite level in plasm of pregnant women who developed transient hypertension later during pregnancy."Reprod Fertil Dev. 11. 5-79 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] S Yura,H Itoh 他7名: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin."J Clin Invest. 105. 749-755 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H Ito 他6名: "Role of the guanylate cyclase system in the regulation of ovine uterine arterial blood flow during pregnancy, a review"Trophoblast Research. 13. 301-309 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] H Itoh, 他4名: "Basic fibroblast growth factor decrease clearance receptor of natriuretic peptide feto-placental artery endothelium"Am J Physiol. 46. R541-R547 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N Sagawa,H Itoh, 他11名: "Leptin is a novel placenta-derived hormone in humans"Taiwanese J Obstet Gynecol. 38. 1-10 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] N Sagawa,H Itoh, 他11名: "Leptin as a novel placenta-derived hormone in humans"Trophoblast research. 13. 25-34 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] KK Okumura,N Sagawa,H Itoh, 他6名: "Platelet activating factor-acetyl hydrolase activity and nitric oxide metabolite level in plasma of pregnant women who developed transient hypertension later during pregnancy"Reprod Fertil Dev. 11(In Press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] S Yura,H Itoh, 他7名: "Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin"J Chin Invest. 105(In Press). (2000)

    • Related Report
      1999 Annual Research Report

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

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