| Project/Area Number |
07457126
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Keio University |
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Principal Investigator |
SARUTA Takao Keio University, School of Medicine, Associate Professor, 医学部, 教授 (70051571)
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| 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)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,600,000 (Direct Cost: ¥3,600,000)
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| Keywords | Postmenopause / Hypertension / Salt sensitivity / Dahl salt-sensitive rats / Pressure natriuresis curve / Intracellular calcium / Protein kinase C / Nitric oxide / NO / 筋小胞体Caポンプ / 更年期高血圧 / 細胞内カルシウム代謝 / 卵巣摘出術 / 圧利尿反応 / 血小板 / エストロゲン / ダールラット |
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| 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.
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