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1996 Fiscal Year Final Research Report Summary

Genetic Background and Underlying Mechanism in the Development of Postmenopausal Hypertension

Research Project

Project/Area Number 07457126
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKeio University

Principal Investigator

SARUTA Takao  Keio University, School of Medicine, Associate Professor, 医学部, 教授 (70051571)

Co-Investigator(Kenkyū-buntansha) SASAKI Takayuki  Keio University, School of Medicine, Research Fellow, 医学部, 助手 (40235255)
HAYASHIDA Tomoko  Keio University, School of Medicine, Research Fellow, 医学部, 助手 (20228604)
OHNO Yoichi  Keio University, School of Medicine, Research Fellow, 医学部, 助手 (10203895)
HAYASHI Koichi  Keio University, School of Medicine, Associate Professor, 医学部, 講師 (80164937)
HAYASHI Matsuhiko  Keio University, School of Medicine, Associate Professor, 医学部, 助教授 (60129608)
Project Period (FY) 1995 – 1996
KeywordsPostmenopause / Hypertension / Salt sensitivity / Dahl salt-sensitive rats / Pressure natriuresis curve / Intracellular calcium / Protein kinase C / Nitric oxide
Research Abstract

Several epidemiological studies have shown that the incidence of cardiovascular disease rapidly increases after menopause. Hypertension is one of the main risk factors for cardiovascular disease, and there are gender differences in its prevalence. However, underlying mechanisms of sexual differences remain unclear. One of the most important clinical characteristics of postmenopausal hypertension is salt sensitivity.
First, we attempted to establish a female salt-sensitive postmenopausal hypertensive model by ovariectomizing Dahl-Iwai salt-sensitive (DS) rats. Ovariectomy aggravated hypertension and platelet aggregation in DS rats. Estrogen supplement improved hypertension and platelet dysfunction. Systolic blood pressure was inversely correlated with 17beta-estradiol level and with uterus weight to body weight ratio.
Second, we investigated the effect of ovariectomy on pressure-natriuresis by in vivo perfusion studies. The pressure-natriuresis relationship was blunted in ovariectomized DS rats.
Third, we examined the effect of ovariectomy on intracellular Ca^<2+>. The internal Ca^<2+> discharge capacity was reduced. Systolic blood pressure was inversely correlated with the internal Ca^<2+> discharge capacity.
Fourth, to clarify how platelet aggregation was enhanced in ovariectomized DS rats, we assessed the changes in platelet aggregation by adding a protein kinase C activator or an inhibitor of nitric oxide synthase. Platelet aggregation was proved to be augmented in ovariectomized DS rats by activating protein kinase C and by suppressing nitric oxide synthesis.
We concluded that ovariectomy enhanced sodium-induced hypertension by blunting the pressure-natriuresis relationship, associated with the decreased internal Ca^<2+> discharge capacity and increased platelet aggregation through protein kinase C activation and the suppression of nitric oxide synthesis in DS rats.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Saruta T et al: "Antihypertensive agents and renal protection:Calcium channel blockers" Kid Int. 49. S52-S56 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi M et al: "Na+-H+-exchanger 3 activity and its gene in the spontaneously hypertensive rat kidney" J Hypertens. 15. 43-48 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hayashi K et al: "Altered myogenic responsiveness of the renal microvasculature in experimental hypertension" J Hypertens. 14. 1387-1401 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohno Y et al: "Genotypes of sarco(endo)plasmic reticulum Ca2+-dependent AT Pase II gene in substrains of spontaneously hypertensive rats" J Hypertens. 14. 287-291 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohno Y et al: "Genetic Linkage of the Sarco(endo)plasmic Reticulum Ca2+-Dependent AT Pase II Gene to Intracellular Ca2+Concentration in the Spontaneously Hypertensive Rat" BBRC. 227. 789-793 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Otsuka K et al: "Blunted Pressure Natriureis in Ovariectomized Dahl-Iwai Salt-Sensitive Rats" Hypertension. 27. 119-124 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saruta T et al: "Antihypertensive agents and renal protecion : Calcium channel blockers" Kid Int. 49. S52-S56 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi M et al: "Na^+-H^+-exchanger 3 activity and its gene in the spontaneously hypertensive rat kidney" J Hypertens. 15. 43-48 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hayashi K et al: "Altered myogenic responsiveness of the renal microvasculature in experimental hypertension" J Hypertens. 14. 1381-1387 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohno Y et al: "Genotypes of sarco (endo) plasmic reticulum Ca^<2+>-dependent ATPase II gene in substrains of spontaneously hypertensive rats" J Hypertens. 14. 287-291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohno Y et al: "Genetic linkage of the sarco (endo) plasmic reticulum Ca^<2+>-dependent ATPase gene to intracellular Ca^<2+> concentration in the spontaneously hypertensive rat" BBRC. 227. 789-793 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Otsuka K et al: "Blunted Pressure Natriureis in Ovariectomized Dahl-Iwai Salt-Sensitive Rats" Hypertension. 27. 119-124 (1996)

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

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Published: 1999-03-09  

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