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1998 Fiscal Year Final Research Report Summary

Molecular biological studies on regulatory systems of the circulation in angiotensinogen gene knockout mice.

Research Project

Project/Area Number 08407020
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYokohama City University

Principal Investigator

UMEMURA Satoshi  Yokohama City University, School of Medicine, Department of Medicine II, Professor, 医学部, 教授 (00128589)

Co-Investigator(Kenkyū-buntansha) KIHARA Minoru  Yokohama City University, School of Medicine, Department of Medicine II, Research Assistant, 医学部, 助手 (60177904)
TAKAGI Nobuyoshi  Yokohama City University, School of Medicine, Department of Medicine II, Assistant Professor, 医学部, 講師 (10163172)
MURAKAMI Kazuo  University of Tsukuba, Institute of Applied Biochemistory, Professor, 応用生物系, 教授 (70110517)
ISHIGAMI Tomoaki  Yokohama City University, School of Medicine, Department of Medicine II, Research Assistant, 医学部, 助手 (50264651)
TAMURA Kouichi  Yokohama City University, School of Medicine, Department of Medicine II, Research Assistant, 医学部, 助手 (40285143)
Project Period (FY) 1996 – 1998
KeywordsRenin Angiotensin System / Angiotensinogen / Gene Targeting / Renin / Angiotensin receptor / Regulation of gene expression / Neuronal nitric oxide synthase
Research Abstract

To clarify the role of renin angiotensin system (RAS) in the regulation of circulating system, in vivo and in vitro studies were performed using angiotensinogen gene knockout mice (Atg ィイD1-ィエD1/ィイD2-ィエD2 ) and it's control mice (Atg ィイD1+ィエD1/ィイD2+ィエD2 ).
(1) Hormonal and electrochemical changes, evalated in the Atg ィイD1+ィエD1/ィイD2+ィエD2 and Atg ィイD1-ィエD1/ィイD2-ィエD2 mice fed salt restricted or salt loading diets as well as normal salt diet, suggested the essential role of RAS in the blood pressure maintenance as well as water electrolyte homeostasis.
(2) In the kidney of Atg ィイD1-ィエD1/ィイD2-ィエD2, we found renal vessel specific changes, such as hyperplasia and/or hypertrophy of vascular smooth muscle cells, multi-layered elastic reduplication in the intima and media of renal vessels, and increasing renin containing cells, suggesting the important role of RAS in the normal differentiation and development of the kidney.
(3) Neuronal type of nitric oxide synthase (N-NOS) in the macula densa of Ang ィイD1-ィエD1/ィイD2-ィエD2 mice is upregulated and inversely regulated by salt intake and this enzyme activity is functionally linked to renal renin production.
(4) In Atg ィイD1-ィエD1/ィイD2-ィエD2 mice, lack of Ang II may upregulated ATィイD21ィエD2-R through translational and/or posttranslational mechanisms in Atg ィイD1-ィエD1/ィイD2-ィエD2 mice.
(5) Studies on stretch-induced MAP kinase activation in Atg ィイD1+ィエD1/ィイD2+ィエD2 cardiac myocytes suggested the importance of cardiac RAS, although Ang II is not indispensable for mechanical stretch-induced activation of MAP kinases in Atg ィイD1-ィエD1/ィイD2-ィエD2 cardiac myocytes. Furthermore we found that cytokine gp 130 may play a role in the stretch-induced MAP kinase activation independently of Ang II in cardiac myocyte.

  • Research Products

    (67 results)

All Other

All Publications (67 results)

  • [Publications] Tamura kouichi: "Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats"Hypertension. 27. 1216-1223 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Modulation of tissue angiotensinogen gene expression in genetically obese hypertensive rats"Am J Physiol. 272. R1704-R1711 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kihara Minoru: "The neuronal isoform of constitutive nitric oxide synthase is up regulated in the macla densa of angiotensinogen gene-knockout mice"Lab invest. 76. 285-294 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura Satoshi: "Plasma angiotensinogen soncentrations in obese patient"Am J Hypertens. 10. 629-633 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura Satoshi: "Distribution of α_<1B>-adrenegic receptor mRNA expression along rat nephron segments"Kidney Int. 51. 1548-1552 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi Daisuke: "Rslationship between angiotensinogen mRNA expression and plasma angiotentinogen in patients with chronic hepatitis"Life Sci. 60. 1623-1633 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nyui Nobuo: "Tissue angioitensinogen gene expression induced by lipopolysaccharide in hypertensive rats"Hypertension. 30. 859-867 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "A novel procimal element mediates the regulation of mouse Ren-1C promoter by retinoblastoma protein in cultured cells"J Biol Chem. 272. 16845-16851 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hibi Kiyoshi: "Angiotensin-converting enzy me gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers"Hypertension. 30. 574-579 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuo Nyui: "Stretch-induced map kinase activation in cardiomy ocytes of angiotensinogen-deficient mice"Bioch Biophy Res Comm. 235. 36-41 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Watanabe Yasujiro: "Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese"Hypertension. 30. 569-573 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura Satoshi: "Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene"Hypertension. 30. 1325-1330 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sumida Yoichi: "Increased cardiac angiotensin II receptors in angiotentinogen-deficient mice"Hypertension. 31. 45-49 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kihara Minoru: "Dietary salt loading decreases the expressions of neuronal-type nitric oxide synthease and renin in the juxtaglomerular apparatus of angiotentinogen gene-knockout mice"J Am Soc Nephrol. 9. 355-362 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura Satoshi: "Endocrinological abnormalities in angiotensinogen-gene knockout mice : studies of hormonal responses to dietary salt loading"J Hypertens. 16. 285-289 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kihara Minoru: "Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice"Kidney Int. 53. 548-555 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kihara Minoru: "Expression of neuronal type nitric oxide synthase and renin in the juxraglomerular apparatus of angiotensin type-la receptor gene-knockout mice"Kidney Int. 53. 1585-1593 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nobuo Nyui: "GP 130 is involved in stretch-induced MAP kinase activation in cardiac myocytes"Bioch Biophy Res Comm. 245. 928-932 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Activaion of angiotensinogen gene in cardiac myocytes by angiotensin II and mechanical stretch"Am J Physiol. 275. R1-R9 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Possible role of c-Jun in transcription of the mouse renin gene"Kidney Int. 54. 382-393 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Effect of genetic deficiency of angiotensinogen on the renin-angiotensin system"Hypertension. 32. 223-227 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hibi Kiyoshi: "Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction"Hypertension. 32. 521-526 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Umemura Satoshi: "Angiotensin-converting enzyme gene polymorphism in Nepal"J Biol Chem. 12. 527-531 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Mechanism of angiotensin II-mediated regulation of fivronectin gene in rat vascular smooth muscle cells"J Biol Chem. 273. 26487-26496 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kihara Minoru: "Angiotensin II inhibits interleukin-lb-induced nitric oxide production in cultured rat mesangial cells"Kidney Int. 55. 1277-1283 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ishigami Tomoaki: "Angiotensinogen gene polymorphism near transcription start site and blood pressure"Hypertension. 34. 430-434 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura kouichi: "Renin-angiotensin sysytem and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats"J Hypertens. 17. 81-89 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石上友章: "眼で見る遺伝子"治療. 78. 2101-2104 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "遺伝子研究の進歩と臨床応用 近未来治療の一端を担う「遺伝子」の行方"治療. 78. 2105-2107 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田村功一: "遺伝子研究の進歩と臨床応用 トピックス 高血圧の遺伝子診断・治療"治療. 78. 2177-2186 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "高血圧と遺伝-ここまで解明されたカテコールアミン関連遺伝子と高血圧"血圧. 4. 536-544 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "高血圧症-分子生物学的研究の最新動向と臨床の進歩 血圧調節因子[生合成系,受容体,受容体後シグナル伝達系]カテコールアミン,ドーパミン"日本臨床. 55. 1915-1922 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 木原実: "傍糸球体装置のレニン産生調節における神経型-酸化窒素合成酵素(N-NOS)の役割 : アンジオテンシノーゲン遺伝子欠損マウスを用いた検討"血圧. 5. 262-271 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 田村功一: "アンジオテンシンIIによる血管平滑筋細胞フィブロネクチン遺伝子発現調節の分子メカニズムについての検討"脈管学. 38. 65-68 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "血管リモデリングと修飾因子 α_1受容体アゴニスト"メディカルレビュー社. 3-18 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石上友章: "血管リモデリングと修飾因子 血管リモデリングと遺伝子因子"メディカルレビュー社. 237-255 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "α交感神経受容体の分子治療学-遺伝子から機能へ- α_2アドレナリン受容体 : 遺伝子とシグナル伝達機構"メディカルレビュー社. 29-40 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "Dahl rat. 続心臓代謝実験法"六法出版社. 247-255 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 石上友章: "降圧薬の上手な使い方 本態性高血圧と遺伝子"南山堂. 241-251 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 梅村敏: "最新高血圧診療-日常診療のバージョンアップのために"南山堂. 1-120 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamura K: "Tissue-specific regulation of angiotensinogen gene expression in spontaneously hypertensive rats"Hypertension. 27. 1216-1223 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Modulation of tissue angiotensinogen gene expression in genetically obese hypertensive rats"Am J Physiol. 272. R1704-R1711 (1997)

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

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umemura S: "Plasma angiotensinogen concentrations in obese patients"Am J Hypertens.. 10. 629-633 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umemura S: "Distribution of αィイD21BィエD2-adrenergic receptor mRNA expression along rat nephron segments"Kidney Int. 51. 1548-1552 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi D: "Relationship between hepatic angiotensinogen in patients with chronic hepatitis"Life Sci. 60. 1623-1633 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nyui N: "Tissue angiotensinogen gene expression induced by lipopolysaccharide in hypertensive rats"Hypertension. 30. 859-867 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "A novel proximal element mediates the regulation of mouse Ren-1C promoter by retinoblastoma protein in cultured cells"J Biol Chem. 272. 16845-16851 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hibi K: "Angiotensin converting enzyme gene polymorphism adds risk for the severity of coronary atherosclerosis in smokers"Hypertension. 30. 574-579 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nyui N: "Stretch-induced map kinase activation in cardiomyocytes of angiotensinogen deficient mice"Bioch Biophy Res Comm. 235. 36-41 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Watanabe Y: "Angiotensin-converting enzyme gene I/D polymorphism and carotid plaques in Japanese"Hypertension. 30. 569-573 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishigami T: "Essential hypertension and 5' upstream core promoter region of human angiotensinogen gene"Hypertension. 30. 1325-1330 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sumida Y: "Increased cardiac angiotensin II receptors in angiotensinogen-deficient mice"Hypertension. 31. 45-49 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kihara M: "Dietary salt loading decreases the expressions of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensinogen gene-knockout mice"J Am Soc Nephrol. 9. 355-362 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umemura S: "Endocrinological abnormalities in angiotensinogen -gene knockout mice: studies of hormonal responses to dietary salt loading"J Hypertens. 16. 285-289 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kihara M: "Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice"Kidney Int. 53. 548-555 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kihara M: "Expression of neuronal nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice"Kidney Int. 53. 1585-1593 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nyui N: "GP130 is involved in stretch-induced MAP Kinase activation in cardiac myocytes"Biochemical and Biophysical Research Communications. 245. 928-932 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Activation of angiotensinogen gene in cardiac myocytes by angiotensin II and mechanical stretch"Am J Physiol. 275. R1-R9 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Possible role of c-Jun in transcription of the mouse renin gene"Kidney Int. 54. 382-393 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Effect of genetic dificiency of angiotensinogen on the renin-angiotensin system"Hypertension. 32. 223-227 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hibi K: "Endothelial nitric oxide synthase gene polymorphism and acute myocardial infarction"Hypertension. 32. 521-526 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Umemura S: "Angiotensin-converting enzyme gene polymorphism in Nepal"J Hum Hypertens. 12. 527-531 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Mechanism of angiotensin II-mediated regulation of fubronectin gene in rat vascular smooth muscle cells"J Biol Chem. 273. 26487-26496 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kihara M: "Angiotensin II inhibits interleukin-1β-induced nitric oxide production in cultured rat mesangial cells"Kidney Int. 55. 1277-1283 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ishigami T: "Angiotensinogen gene polymorphism near transcription start site and blood pressure. Role of a T-to-C transition at Intron I"Hypertension. 34. 430-434 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamura K: "Renin-angiotensin system and fibronectin gene expression in Dahl Iwai salt-sensitive and salt-resistant rats"J Hypertens. 17. 81-89 (1999)

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

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Published: 2001-10-23  

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