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Molecular Research of the Etiology and Treatment of Hypertension

Research Project

Project/Area Number 04404044
Research Category

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

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

Principal Investigator

OGIHARA Toshio  Osaka University, Medical School, Department of Geriatric Medicine, Associate Professor, 医学部, 教授 (60107042)

Co-Investigator(Kenkyū-buntansha) RAKUGI Hiromi  Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (20252679)
HIGAKI Jitsuo  Osaka University, Medical School, Department of Geriatric Medicine, Assistant Pr, 医学部, 助手 (70189744)
MIKI Tetsuro  Osaka University, Medical School, Department of Geriatric Medicine, Lecturer, 医学部, 講師 (00174003)
MIKAMI Hiroshi  Osaka University, Medical School, Department of Geriatric Medicine, Associate Pr, 医学部, 助教授 (80173996)
森本 茂人  大阪大学, 医学部, 講師 (20150336)
長野 正広  大阪大学, 医学部, 助手 (50228045)
福尾 恵介  大阪大学, 医学部, 助手 (40156758)
池上 博司  大阪大学, 医学部, 助手 (20221062)
東森 浩一  大阪大学, 医学部, 助手 (70238278)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥20,500,000 (Direct Cost: ¥20,500,000)
Fiscal Year 1994: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1993: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1992: ¥10,500,000 (Direct Cost: ¥10,500,000)
KeywordsHYPERTENSION / GENE / MOLECULAR GENETICS / GENE DIAGNOSIS / GENE THERAPY / MOLECULAR BIOLOGY / GENE ANALYSIS / 遺伝子解析 / 分離生理学 / 高血圧症 / 高血圧自然発症ラット / 多因子疾患 / フォスフォリパーゼ / 遺伝子導入
Research Abstract

To investigate the molecular etiology of hypertension, we have conducted genetic screening of the spontaneously hypertensive rat (SHR). We have detected so far two loci which are related with blood pressure determination : one is the NPY gene on chromosome 4 which induces blood pressure elevation, and the other is the PLCdelta _1 gene on chromosome 8 with hypotensive effect. We also showed that the angiotensin converting enzyme gene on chromosome 10 is related with salt-sensitivity of stroke-prone SHR,and that the mutation of adrenal P450_<11beta> gene may be responsible for the salt-resistance of Dahl's saltresistant rats. These results suggest that the mosaic of multiple genes contributes to the degermination of the blood pressure level.
On the other hand, in the human study using Japanese population, we confirmed significance of hypertensinogenic T235 variant of the angiotensinogen gene, which has been formerly reported in European Caucasians by Jeunemaitre et al. Although we failed … More to prove that the insertion/deletion polymorphism of angiotensin-converting enzyme associates with blood pressure in Japanese, we demonstrated that the deletion polymorphism of angiotensin converting enzyme gene could be a potent risk factor for not only myocardial infarction but also restenosis after percutaneous transluminal angioplasty in Japanese subjects.
Using an efficient and nontoxic in vivo gene transfer method (HVJ-liposome), we produced a hypertensive model rat that is dependent on human renin. The elevated blood pressure was normalized by the intravenous administration of specific human renin inhibitor. Next, HVJ-liposomes containing oligonucleotide complementary to rat angiotensinogen gene were injected into liver. The blood pressure of the rat treated with HVJ-liposome complexed with antisense oligomer decreased. These results showed that the HVJ-liposome could be potentially a good tool for the study of the renin-angiotensin system and a furture gene therapy for hypertension. Less

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Kamitani A.: "Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese." Journal of Human Hypertension. 8. 521-524 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ohishi M.: "Association between deletion polymorphism of the angiotensin converting-enzymegene and left ventricular hypertrophy" New England Journal of Medicine. 331. 1097-1098 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morishita R: "Intimal hyperplasia after vascular injury is inhibited by antisense cdk2 kinase oligonucleotides." Journal of Clinical Investigation. 93. 1458-1464 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Morishita R.: "Autocrine and paracrine effects of atrial natriuretic peptide gene transfer on vascular smooth muscle and endothellal cellular growth." Journal of Clinical Investigation. 94. 824-829 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shi S.J.: "Augmentation by converting enzyme inhibition of accelerated endothelial release from rat mesenteric artery following nephrectomy." Biochemical Biophysical Research Communications. 202. 246-251 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yo Y.: "Effects of age and hypertension on autonomic nervous regulation during passive head-up tilt." Hypertension. 23. 82-86 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Katsuya, T.: "A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat." Biochem Biophys Res comm. 192. 261-267 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Matsukawa, N., Nonaka, Y.: "Higaki, J., et al.Dahl's saltresistant normotensive rat has mutations in cytochrome p450 (11beta), but the salt-sensitive hypertensive rat does not." J Biol Chem. 268. 9117-9121 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ooishi M., Fujii K., Minamino T., et al.: "A potent genetic risk factor for restenosis." Nature Genetics. 5. 324-325 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Zhao Y., Higashimori K., Higaki J., et al.: "Significance of the deletion polymorphism of the angiotensin converting enzyme gene as a risk factor for myocardial infarction in Japanese." Hypertens Res. 17. 55-57 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kamitani, A.: "Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese." J Human Hypertens. 8. 521-524 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kamitani A.: "Association analysis of a polymorphism of the angiotensinogen gene with essential hypertension in Japanese.21GC01:Journal of Human Hypertension" 8. 521-524 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Ohishi M.: "Association between deletion polymorphism of the angiotensin convertingenznme gene and left ventricular hypertrophy." New England Journal of Medicine. 331. 1097-1098 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morishita R.: "Intimal hyperplasia after vascular Injury inimhibited by antisense cdk2 kinase otigonucleotldes." Journal of Clinical Investigation. 93. 1458-1464 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Morishita R.: "Autocrlre and paracrine effects of atrial natrluretlc peptide gene transfection on vascupar smooth muscle and endothelial cellular growth." Journal of Clinical Investigation. 94. 824-829 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shi S.J.: "Augmentation by converting enzyme inhibition of a ccelerated endothelial release from rat mesenteric artery following nephrectomy." Biochemical Biophysical Research Communcations. 202. 246-251 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yo Y.: "Effects of age and hypertension onautonomic nervous regulation during passive head-up tilt." Hypertension. 23. 82-86 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Katsuya T.,et al.: "A neuropeptide Y locus on chromosome 4 cosegregates with blood pressure in the spontaneously hypertensive rat." Biochemical Biophysical Research Communications. 192. 261-267 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Matsukawa N.,et al.: "Dahl's salt-resistant normotensive rat has mutations in cytochrome P450(11β),but the salt-sensitive hypertensive rat does not." Journal of Biological Chemistry. 268. 9117-1921 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Morishita R.,et al.: "Discrepancy between renin mRNA and plasma renin level in angiotensinconverting enzyme inhibitor-treated rats." Clinical and Experimental Pharmacology and Physiology. 20. 135-140 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohishi,M..et al.: "A potent genetic risk factor for restenosis." Nature Genetics. 5. 325-326 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tomita N.,et al.: "Hypertensive rats produced by in vivo introduction of human renin gene." Circulation Research. 73. 898-905 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yu H.,et al: "The role of activated vascular anglotensin II generation in vascular hypertrophy in one-kidney,one clip hypertensive rats." Journal of Hypertension. 11. 1347-1355 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Higashimori K,Higaki J Miki T,Kamitani A,Mkkani H Kumahara Y,Ogihara T: "Analysis of the apolipoprotein B3'hypervariable region in patients with essential hypertension." Clinical and Experimental Pharmacology and Physiology. 19. 21-23 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katsuya T,Higaki J,Miki T Kohara K,Yagisawa H,Tanase H Mikami H,Serikawa t,Nojima H Ogihara T.: "Hypotensive efect associated with a phospholipase C-di mutation in the spontaneously hypertensive rat." Biochemical Biophysical Research Communication. 187. 1359-1366 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Katsuya T,Gigaki J,Miki T Nakura J,Ikegame H,Morishita R,Nagano M,Hihashimori K,Pgihara: "Substrain comparison of genetically hypertensive rat using DNA fingerprinting,and genetic analysis of blood pressure in the inbred rats." The Tohoku Journal of Experimental Medicine. 165. 253-260 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Nagano M,Higaki J,Nakamura F,Higashimori K,Nagani N Mikami H,Ogihara T: "Role of cardiac angiotensin II in isoproterenolinduced left ventricalar hypertrophy" Hypertension. 19. 708-712 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tateyama H,Hino J,Minamini N,Kangawa K,Minamini T,Sakai t,Ogihara T,Matsuo H: "Concentrations and molecular forms of human brain natriuretic peptide in plasma." Biochemical Biophysocal Research Communications. 185. 760-767 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Tomita N, Higaki J,Morishita R,Kato K,Mikami H,Kaneda Y,Ogihara T: "Direct in vivo gene introduction into rat kidney." Biochemical Biohysical Research Communications. 186. 129-134 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2017-10-06  

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