| Project/Area Number |
09558084
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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 | 展開研究 |
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| Research Field |
Functional biochemistry
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| Research Institution | University of Tsukuba |
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Principal Investigator |
FUKAMIZU Akiyoshi University of Tsukuba, Institute of Applied Biochemistry, Professor, 応用生物化学系, 教授 (60199172)
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| Co-Investigator(Kenkyū-buntansha) |
菅谷 健 田辺製薬株式会社, 医薬拓新研究所, 研究員
HORIGUCHI Hisashi Molecular Pathology Center, Ibaraki Prefectural University of Health Sciences, Reseach Associate, 保健医療学部, 助手 (30238795)
NAKAGJIMA Toshihiro University of Tsukuba, Institute of Applied Biochemistry, Assistant Professor, 応用生物化学系, 講師 (90260752)
SUGAYA Takashi Discovery Research Laboratory, Tanabe Seiyaku, Researcher
杉山 文博 筑波大学, 基礎医学系, 講師 (90226481)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 1999: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1997: ¥6,600,000 (Direct Cost: ¥6,600,000)
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| Keywords | angiotensin / pregnancy / renin / blood pressure / hypertension / transgenic mice / knock-out mice / hypertrophy |
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| Research Abstract |
Pregnancy-induced hypertension (PIH), the commonest and most serious complications of pregnancy, usually becomes apparent in late pregnancy, the pathophysiology of which has remained elusive (1). Here, we show that later in pregnancy blood pressure is dramatically elevated in transgenic female mice expressing human angiotensinogen only when mated with male mice carrying the human renin gene, which is due to the secretion of feto-placental human renin into the maternal circulation. The observed transient elevation of blood pressure was sharply returned to the non-pregnant state after delivery. Histopathologic examinations revealed uniform enlargement of glomeruli associated with increase in urinary protein excretion, myocardial hypertrophy and necrosis and edema in placenta. These results clearly demonstrate that PIH that caused maternal morbidity and mortality is triggered by the combinatorial action of feto-placental renin genetically derived from male mice with maternal angiotensinogen in transgenic mice.
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