1999 Fiscal Year Final Research Report Summary
A new mouse model for pregnancy-induced hypertension.
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 |
Section | 展開研究 |
Research Field |
Functional biochemistry
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Research Institution | University of Tsukuba |
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
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Project Period (FY) |
1997 – 1999
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Keywords | angiotensin / pregnancy / renin / blood pressure / hypertension / transgenic mice / knock-out mice / hypertrophy |
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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[Publications] Ishida, J., Asada, S., Daitoku, H., Fujiwara, K., Kon, Y., Sugaya, T., Murakami, K., Nakajima, T., Kasuya, Y., and Fukamizu, A.: "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells"Int. J. Med.. 3. 263-270 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Hisada, Y., Sugaya, T., Yamanouchi, M., Uchida, H., Fujimura, H., Sakurai, H., Fukamizu, A., and Murakami, K.: "Angiotensin II plays a pathogenic role in immune-mediated renal injury in mice"J. Clin. Invest.. 103. 627-635 (1999)
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[Publications] Nishijo, N., Takamine, S., Sugiyama, F., Kimoto, K., Taniguchi, D., Horiguchi, H., Ogata, T., Murakami, K., Fukamizu, A., and Yagami, K.: "Vascular Remodeling in Hypertensive Transgenic Mice"Exp. Anim.. 48. 203-208 (1999)
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[Publications] Tanimoto, Y., Tanimoto, K., Sugiyama, F., Horiguchi, H., Murakami, K., Yagami, K., and Fukamizu, A.: "Male Sterillity in Transgenic Mice Expressing Activin βA Subunit Gene in Testis"Biochem. Biophys. Res. Commun.. 259. 699-705 (1999)
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[Publications] Tadahiko Nishi, Atsushi Moriguchi, Ryuichi Morishita, Kazuo Yamada, Shigefumi Nakamura, Naruya Tomita, Yasufumi Kaneda, Akiyoshi Fukamizu, Hiroshi Mikami, Jitsuo Higaki, Toshio Ogihara: "Angiotensinogen Gene-Activating Elements Regulate Blood Pressure in the Brain"Circ Res.. 85. 257-263 (1999)
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「研究成果報告書概要(欧文)」より
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