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Molecular mechanism of hypertension on pregnant transgenic mice.

Research Project

Project/Area Number 09306024
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied molecular and cellular biology
Research InstitutionFOUNDATION FOR ADVANCEMENT OF INTERNATIONAL SCIENCE (1999)
University of Tsukuba (1997-1998)

Principal Investigator

MURAKAMI Kazuo  Foundation for Advancement of International Science Executive Director, 専任研究員 (70110517)

Co-Investigator(Kenkyū-buntansha) HORIGUCHI Hisasi  Medical Univ. Ibaraki Pref., Instructor, 保健医療学部, 助手 (30238795)
KASUYA Yoshitoshi  Basic Medicine, Univ. of Tsukuba, Assist. Prof., 基礎医学系, 講師 (70221877)
FUKAMIZU Akiyoshi  Inst. Of Applied Biochem., Univ. of Tsukuba, Prof., 応用生物化学系, 教授 (60199172)
杉山 文博  筑波大学, 基礎医学系, 講師 (90226481)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥10,800,000 (Direct Cost: ¥10,800,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥8,100,000 (Direct Cost: ¥8,100,000)
KeywordsTsukuba hypertensive mouse / malignant hypertension / Vascular remodeling / renin-angiotensin system / transgenic mouse / 腎臓 / 大動脈瘤 / 動脈硬化症 / コレステロール / 脂肪 / アンギオテンシンII / 受容体 / レニン / 高血圧 / アンジオテンシノーゲン / 妊娠 / トランスジェニックマウス / アンジオテンシンII / 臓器傷害
Research Abstract

(1) The Tsukuba hypertensive mouse as a model of human malignant hypertension
The renin-angiotensin, system has a pivotal role in hypertension. The Tsukuba hypertensive mouse (THM; a transgenic mouse carrying human genes for both renin and angiotensinogen) was generated to allow further examination of the renin-angiotensin system in a variety of pathologic conditions. We evaluated the development of renal lesions in these mice and in controls by morphometric, immunohistochemical and ultra-structural methods. Blood pressure was significantly higher in THM than in control mice; 1 year after birth, it was approximately 40 mmHg higher. The kidney-to-body weight ratio was also higher in THM than in control. Morphometrical analysis revealed that the glomerular sclerosis index was significantly elevated in THM with 10% of the glomeruli sclerotic at 18 months. The grade of vascular lesion and the frequency of fibronoid arteritis of the kidney exhibited the same tendency as the glomerular sclerosis index. Light and electron microscopy revealed significant fibrinoid arteritis of the kidney in THM and also "onion skinning" , both pathognomonic for malignant nephrosclerosis. THM may be an excellent model of human malignant hypertension.
(2) Vascular remodeling in hypertensive transgenic mice
We physiologically and histopathologically analyzed vascular damage due to hyper' tension and vascular remodeling in hypertensive transgenic mice (THM). Pubertal(8-week -old) THM already had hypertension similar to blood pressure in adult THM due to an enhanced renin angiotensin system (RAS). They progressively developed remarkable vascular hypertrophy composed of dedifferentiation of vascular smooth muscle cells (VSMCs) and extracellular matrix accumulation in the thoracic aorta, and VSHC hyperplasia was predominant in the abdominal aorta. THM are therefore a useful animal model for studying vascular remodeling mediated by enhanced RAS.

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] K. Tamura et al.: "Modulation of tissue angiotesinogen gene expression in genetically obese hypertensive rats"Am. J. Physiol.. 272. 1704-1711 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F. Sugiyama et al.: "Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system"Laboratory Investigation. 76. 835-842 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F. Sugiyama et al.: "Speedy backcrossing through in vitro fertilization using prepubertal superovulation and neonatal deth dependent on genetic background in angiotensinogen-deficient mice"Lab. Anim. Sci.. 47. 545-548 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Nishijo et al.: "Salt- sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II."Lab. Invest.. 78. 1059-1066 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T. Shimokama et al.: "The Tsukuba hypertensive mouse as a model of human malignant hypertension"Virchows Arch.. 432. 169-175 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Kihara et al.: "Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus"J. Am. soc. Nephrol.. 9. 355-362 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S. Umemura et al.: "Endocrinological abnormalities in angiotensinogen-gene knockout mice : studies of hormonal responses to dietary salt loading"J. Hypertension. 16. 285-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N. Nishijo et al.: "Vascular remodeling in hypertensive transgenic mice"Exp. Anim.. 48. 203-208 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J. Ishida et al.: "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin opitope in cultured cells"International J. Molecular Medicine. 3. 263-270 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K. Murakami et al.: "Hypertension induced in pregnant mice by paternal renin and maternal angiotensinogen"Hypertension in Pregnancy. 19. 1-2 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 村上和雄: "発生工学的手法を用いた高血圧モデル動物の作製とその病態解析"Heart Disease. 22. 114-120 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 深水昭吉: "アジオテンシン情報伝達系の発生工学的研究"生化学. 69. 991-1002 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Tamura et al.: "Modulation of tissue angiotensinogen gene expression in genetically obese hypertensive rats."Am. J. Physiol.. 272. 1704-1711 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F.Sugiyama et al.: "Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system."Laboratory Investigation. 76. 835-842 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] F.Sugiyama et al.: "Speedy backcrossing through in vitro fertilization using prepubertal superovulation and neonatal deth dependent on genetic background in angiotensionogen-deficient mice."Lab. Anim. Sci.. 47. 545-548 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Nishijo et al.: "Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II."Lab. Invest.. 78. 1059-1066 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Shimokama et al.: "The Tsukuba hypertensive mouse as a model of human malignant hypertension."Virchows Arch.. 432. 169-175 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Kihara et al.: "Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus."J. Am. Soc. Nephrol.. 9. 355-362 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Umemura et al.: "Endocrinologicaol abnormalities in angiotensiogen-gene knockout mice: studies of hormonal responses to dietary salt loading."J. Hypertension. 16. 285-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Nishijo et al.: "Vascular remodeling in hypertensive transgenic mice."Exp. Anim.. 48. 203-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J.Ishida et al.: "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells"Int'l. J. Molecular Med.. 3. 263-270 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Murakami et al.: "Hypertension induced in pregnant mice by paternal renin and maternal angiotensionogen."Hypertension in Pregnancy. 19. 1-2 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] K.Kihara et al.: "Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthase and renin in the juxtaglomerular apparatus"J.Am.Soc.Nephrol.. 9. 355-362 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] S.Umemura et al.: "Endocrinological abnormalities in angiotensinogen-gene knockout mice : studies of hormonal responses to dietary salt loading"J.Hypertens.. 16. 285-289 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Nishijo et al.: "Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angioptensin II"Lab.Invest.. 78. 1059-1066 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] N.Nishijo et al.: "Vascular remodeling in hypertensive transgenic mice"Exp.Anim.. 48. 203-208 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Tamura et al.: "Modulation of tissue angiotensinogen gene expression in genetically obese hypertensive rats." Am.J.Physiol.272. 1704-1711 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Sugiyama et al.: "Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated ranin-angiotensin system." Laboratory Investigation. 76. 835-842 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] F.Sugiyama et al.: "Speedy backcrossing through in vitro fertilization using prepubertal superovulation and neonatal deth dependent on genetic background in angiotensinogen-deficient mice." Lab.Anim.Sci.47. 545-548 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] N.Nishijo et al.: "Salt-sensitive aortic aneurysm and rupture in hypertensive transgenic mice that overproduce angiotensin II." Lab.Invest.78. 1059-1066 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] J.Ishida et al.: "Expression and characterization of mouse angiotensin II type 1a receptor tagging hemagglutinin epitope in cultured cells." International J.Molecular medicine. 3. 263-270 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Bohlender,J.: "High renin hypertension in transgenic rats." Hypertension. 29[part 2]. 428-434 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kihara,M.: "The neuronal isoform of constitutive nitric oxide synthase is upregulated in the macula densa of angiotensinogen gene-knockout mice." Lab.Invest.76. 285-294 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugiyama,F.: "Acceleration of atherosclerotic lesions in transgenic mice with hypertension by the activated renin-angiotensin system." Lab.Invest.76. 835-842 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kakinuma,Y.: "Anti-apoptotic action of angiotensin fragments to neuronal cells from angiotensinogen knock-out mice." Neurosci.Lett.232. 167-170 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugiyama,F.: "Speedy backcrossing through in vitro fertilization using prepubertal superovulation and neonatal death dependent on genetic background in angiotensinogen-deficient mice." Lab. Amin.Sci.47. 545-548 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yanai,K: "Molecular variation of human angiotensinogen core promoter element located between TATA box and transcription initiation site affects its transcriptional activity." J.Biol.Chem.272. 30558-30562 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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