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Molecular pharmacological analysis of role of angiotension II in cardio vascular damage

Research Project

Project/Area Number 07672471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 応用薬理学・医療系薬学
Research InstitutionOSAKA CITY UNIVERSITY

Principal Investigator

KIM Shokei  Osaka City University, Medical School, Lecturer, 医学部, 講師 (10195414)

Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1995: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsAngiotensin II / AT_1 receptor / Cardiac hypertrophy / cardiac failure / gene expression / vascular thickening / AP-1 / fibronectin / アンジオテンシン / 降圧薬 / コラーゲン / 遺伝子 / 心筋梗塞
Research Abstract

Cellular phenotypic modulation and the enhanced gene expression of various growth factors and extracellular matrix play an important role in the development of pathologic cardiac hypertrophy and vascular thickening. Pathologic cardiac hypertrophy is accompanied not only by myocyte hypertrophy but also by the shift of myocytes to a fetal phenotype and interstitial fibrosis, which contribute to the modulation of cardiac performance and the onset of heart failure. In this study, we examined the role of angiotensin II in cardiovascular diseases. In hypertensive rats, AT1 receptor antagonist significantly regresses cardiac hypertrophy. Furthermore, AT1 receptor antagonist prevents the shift of cardiac myocytes from an adult to a fetal phenotype, and suppresses the expression of fibrosis-related genes such as collagen and TGF-beta1. These effects of AT1 receptor antagonist on cardiac hypertrophy and gene expressions are more potent than those of calcium channel antagonist. Thus, local renin-angiotensin system is responsible for pathologic cardiac hypertrophy and remodeling. Balloon injury dramatically increases the expression of proto-oncogenes, growth factors and extracellular matrix components. AT1 receptor antagonist can prevent neointimal thickening in balloon-injured artery of rats, thereby supporting the critical role of AT1 receptor in vascular thickening. This anti-proliferative effect of AT1 receptor antagonist is associated with the inhibition of the increased expression of c-fos, c-jun, Egr-1 and fibronectin in injured artery. Thus, AT1 receptor antagonist in vivo potently inhibits either the growth-related gene and extracellular matrix gene expressions or the celluar phenotypic modulation. These cellular and molecular effects of AT1 receptor antagonist may partially contribute to the beneficial effects on cardiovascular diseases.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] Kim et al.: "Effects of an AT1 receptor antagonist,an ACE inhibitor and a calcium channel antagonist・・・" British Journal of Pharmacology. 118. 549-556 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohta et al.: "Contribution of local renin-angiotensin system to cardiac hypertrophy,phenotypic modulation・・・" Circulation. 94. 785-791 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohta et al.: "Role of angiotensin-converting enzyme,adrenergic receptors,and blood pressure in cardiac gene・・・" Hypertension. 28. 627-634 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 金勝慶他: "レニン-アンジオテンシン系による循環器障害のメカニズム" 医学のあゆみ. 179. 496-497 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kim, S., Ohta, K., Hamaguchi, A., Yukimura, T., Miura, K,Iwao, H.: "Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats." Br J Pharmacol. 118. 549-556 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohta, K., Kim, S., Iwao, H.: "Role of angiotensin-converting enzyme, adrenergic receptors and blood pressure in cardiac gene expression of spontaneously hypertensive rats during development." Hypertension. 28. 627-634 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ohta, K., Kim, S., Wanibuchi, H., Ganten, D., Iwao, H.: "Contribution of local renin-angiotensin system to cardiac hypertrophy, phenotypic modulation and remodeling in TGR (mRen2) 27 transgenic rats." Circulation. 94. 785-791 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kim et al.: "Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagnist…" British Journal of Pharmacology. 118. 549-556 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohta et al.: "Contribution of local renin-angiotensin system to cardiac hypertrophy, phnotypic modulation…" Circulation. 94. 785-791 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohta et al.: "Role of angiotensin-converting enzyme, adrenergic receptors, and blood pressure in cardiac gene…" Hypertension. 28. 627-634 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 金勝慶他: "レニン-アンジオテンシン系による循環器障害のメカニズム" 医学のあゆみ. 179. 496-497 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kim,Shokei: "Effects of an AT1 receptor antagonist" British Journal of Pharmacology. (印刷中).

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2021-10-08  

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