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Study on the Pathogenesis and Prognostic Factors in Hypertension Applying Molecular Biology Techniques.

Research Project

Project/Area Number 01440043
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionOsaka City University Medical School

Principal Investigator

TAKEDA Tadanao  Osaka City University Medical School, First Department of Internal Medicine, Professor, 医学部, 教授 (50010129)

Co-Investigator(Kenkyū-buntansha) NEGORO Nobuo  Osaka City University Medical School, First Department of Internal Medicine, Ins, 医学部, 助手 (80180701)
KOHNO Masakazu  Osaka City University Medical School, First Department of Internal Medicine, Ass, 医学部, 講師 (20153489)
KANAYAMA Yoshiharu  Osaka City University Medical School, First Department of Internal Medicine, Ass, 医学部, 講師 (60106341)
TANABE Kazuyuki  Osaka Engineering College, Department of Biology, Associate Professor (40047410)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥22,600,000 (Direct Cost: ¥22,600,000)
Fiscal Year 1991: ¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1990: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 1989: ¥14,600,000 (Direct Cost: ¥14,600,000)
KeywordsProtein kinase C / Spontaneously hypertensive rats / Phospholipase C / Restriction fragment length polymorphism / Platelet-derived growth factor A / Aorta / 高血圧 / 自然発症高血圧ラット / 血小板由末成長因子(PDGFーA) / 高血圧自然発症ラット(SHR) / WKYラット / 遺伝子クロ-ニング / Restriction fragment length polymorphism(RFLP) / ミオシン軽鎖 / 血小板 / リン酸化 / フオスフォライペ-スC / クロ-ニング
Research Abstract

(1) Protein kinase C (PKC) activity in aorta of spontaneously hypertensive rats (SHR) was elevated compared with WKY rats or enalapril-treated SHR and was closely associated with blood pressure (r=0.84, p<0.001). PKC-alpha protein (74k, 77k) and PKC-alpha mRNA were increased in SHR aorta compared with that in WKY and reversed by enalapril treatment. Thus, PKC protein synthesis is increased in SHR aorta and can be modulated by hypotensive treatment. (2) Restriction fragment length polymorphism (RFLP) of phospholipase C (PLC)-alpha, -beta, -gamma_1, -gamma_2, -delta gene in WKY, SHR and SHRSP was investigated. RFLP in PLCalpha and -beta gene was found between SHRSP and SHR, WKY. RFLP in PLC-gamma_1 gene was found among SHRSP, SHR and WKY. No RFLP was found in PLC-gamma_2 gene. RFLP was also found between SHRSP, SHR, and WKY. (3) Gene expressions of plateletderived growth factor (PDGF)-A, PDGF-B, IL-6, TGF-beta were detected in aorta of SHR. PDGF-A was most abundantly expressed in aorta of SHR when compared with those in WKY in any age examined (4, 8, 15, 54-week-old). These results suggest that PDGF-A is important in the pathogenesis of vascular hypertrophy in hypertension.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Takori K,Inariba H,Itoh S.Inoue T,Kanayama Y,Takeda T,: "Chronic antihypertensive drug treatment decreases protein KinaseC actiity in platelets in platelcts from SHR." Chinical and Expprimental Hypprtenston. A12. 1063-1075 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Minami M,Kanayama Y,Inariba H,Negoro N,Inoue T,Takeda T.: "Angiotensim II induced biphasic inositol 1,4,5-triphosphate response in rat vascular smooth muscle cells." European Journal of Pharmacology-Molocalar Pharmacolgy see.208. 93-95 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Inariba H,kanayama Y,Takaori K,Negoro N,Inoue T,Takeda T,: "Increased Na^+/H^+ exchange activity in vascular smooth muscle cells of spotuneously hypertensiue rats and possible involvament of protein KinaseC." Chinical and Experimoutal pharacolgy and Physiology. 19. (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 武田 忠直: "細胞分子レベルからみた高血圧研究の一断章" 高血圧. 13. 91-101 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Nanayama Y,Inariba H,Negoro N,Okamura M,Inoue T,Takeda T,: "Blood pressure is associated with protein kinase C activity in aortic smooth muscle cells from spontaneously hypertesiue rats" Circulation. 82. III-232 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Negoro N,Kanayama Y,Inariba H,Okamura M,Inoue T,Takeda T.: "Restriction fragment length polymorshisns for rat phospholipaseC α gene in spontaneously hypertensiue rats," Journal of Hypertension. 8(suppl). 570 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takaori K. Inariba H. Itoh S. Inoue T. Kanayama Y. Takeda T.: "Chronic antihypertensive drug treatment decreases protein kinase C activity in platelets from SHR." Clin. Exp. Hypertension. A 12. 1063-1075 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Minami M. Kanayama Y. Inariba H. Negoro N. Inoue T. Takeda T.: "Angiotensin II induced biphasic inositol 1, 4, 5-triphosphate response in rat vascular smooth muscle cells." Eur. J. Pharmacol. -Mol. Pharmacol Sec.208. 93-95 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Inariba H. Kanayama Y. Takaori K. Negoro N. Inoue T. Takeda T.: "Increased Na/H exchange activity in vascular smooth muscle cells of spontaneously hypertensive rats and possible involvement of protein kinase C" Clin. Exp. Pharmacol. Physiol.19. (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Takeda Tadanao: "A facet of cellular and molecular hypertension research. (in Japanese)" Kouketsuatu. 13. 91-101 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Kanayama Y. Inariba H. Negoro N. Okamura M. Inoue T. Takeda T.: "Blood pressure is associated with protein kinase C activity in aortic smooth muscle cells from spontaneously hypertensive rats." Circulation. 82. III-232 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Negoro N. Kanayaam Y. Inariba H. Okamura M. Inoue T. Takeda T.: "Restriction fragment length polymorphism for rat phospholipase C gamma gene in spontaneously hypertensive rats." J. Hypertension. 8 (Suppl). S70 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 武田 忠直: "細胞分子レベルからみた高血圧研究の一断章" 高血圧. 13. 91-101 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Ninami M;Kanayama Y;Inariba H;Netoro N;Inoue T;Takeda T.: "AngiotensinII induced diphasic inositolー1,4,5ーtinphosphate response in rat vascular smooth muscle cells" European Journal 競f pharmacologyーMoleculan Pharmacll. 208. 93-95 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] 根来 伸夫,金山 良春,岡林 幹夫,岩井 潤子,井上 隆智,武田 忠直: "高血圧自然発症ラットの大動脈における成長因子の遺伝子発現についての検討" 高血圧. 14. 56 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Negoro N;Kanayama Y;Okamura M;Inoue T;Takeda T.: "Growth factor gene expression in aorta of spontaneously hypostensue rats." Circulation. 84. II-560 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Imariba H;Kanayama Y;Takaor K;Nobuo N;Inoue T;Takeda T.: "Increasecl Na^+/H^+ exchange activity in vascular smooth muscle cells of spontaneously hypentersive rats and possible involvement of protein kinase C." Clinical Explrimental Pharmacology and physiology. 9. (1992)

    • Related Report
      1991 Annual Research Report
  • [Publications] Kanayama,Y.Inariba,H.Takaori,K.Itoh,S.Takeda T.: "Incneased phosphorylation of myosim light chain in platelets of spontaneously hypertensine rats." Hypertension. 12. 356 (1988)

    • Related Report
      1990 Annual Research Report
  • [Publications] Takaori K.Inariba H.Itoh S.Inoue T.Kanayama Y.Takeda T.: "Chronic antihypertensive drug treatment decreases Protein kinase C activity in plateles from SHR." Clinical & Experimental Hypertension. A12. 1063-1075 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kanayama Y,Takaori K,Inariba H,Negoro N,Inoue T,Takeda T.: "Hypotensive treatment modulates phosphorylation of myosin light chain in platelets of spontaneously hypertensive rats" Circulation. 80. II22 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Negoro N,Kanayama,Y,Inariba H,Okamura M,Inoue T,Takeda T.: "Endothehin modulated cーmyc protooncogene expression in cultussl aortic smooth muscle cells from spontaneously hypertensive rats." Hypertension. 14. 340-341 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kanayama,Y.Inariba H,Negoro N,Okamura M,Inoue T,Takeda T.: "Blood pressure is associated with proteinkinase C activity in aortic smooth muscle cells from spontaneously hypertensive rats" circulation. 82. III-232 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Negoro N,Kanayama Y,Inariba H,Okamura M,Inoue T,Takeda T.: "Restriction fragment length polymorphisms for rat phospholipase Cーγ gene in spontaneously hypertensive rats." J.Hypertension. 8(sup13). S70 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Kanayama Y.,Inariba H.,Takaori K.,Itoh S.,Takeda T.: "Increased phosphorylation of myorin light chain in platelets of spontaneously by peitenoiue rats." Hypertension. 12. 356 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Takaori K.,Inariba H.,Itoh S.,Inoue T.,Kanayama Y.,Takeda T.: "Chronic antihypertensive drug treatment decieases Protein kinase C activity in plateles from SHR." Clinical&Experimental Hypertension,in press. (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Kanayama Y.,Takaori K.,Inariba H.,Negoro N.,Inoue T.,Takeda T.: "Hypotensive treatment modulates phosphorylation of myosin light chain in platelets of spontaneously hypertensive rats." Circulation. 80. II22 (1989)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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