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Pathosignificance of cardiac aldosterone synthesis in heart failure

Research Project

Project/Area Number 13670729
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

YOSHIMURA Michihiro  Kumamoto University, Department of Cardiovascular Medicine, Associate Professor, 医学部, 助教授 (30264295)

Co-Investigator(Kenkyū-buntansha) OGAWA Hisao  Kumamoto University, Department of Cardiovascular Medicine, Professor, 医学部, 教授 (50177135)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsaldosterone / heart failure / hypertension / neurohumoral factor / natriuretic peptide / gene / angiotensin / ACE / 神経液体因子 / 心臓カテーテル検査 / ACE阻害薬 / 前室間静脈 / 冠静脈洞
Research Abstract

Extra-adrenal aldosterone synthase system has been closed-up recently and we also showed that aldosterone was synthesized and secreted from human failing or hypertensive heart. And we recently showed that cardiac aldosterone synthesis is suppressed by ACE inhibitor.
Still more detailed examination was performed about the human cardiac aldosterone synthesis. The cardiac tissue was extracted from the autopsy of patients with heart failure or non-heart failure and we examined gene expression of CYP11B2, aldosterone synthase. Since the expression of CYP11B2 was very small, we could not detect them by usual real-time RT-PCR method. Then, we newly modified real-time RT-PCR and we were able to detect the gene expression and quantified them. Consequently, the gene expression of CYP11B2 was up-regulated in the failing heart compared with the non-failing heart.
Next, the inhibitory effect of natriuretic peptide (NP) on cardiac aldosterone synthesis was examined using neonatal rat cardiocyte culture system. By blocking endogenous natriuretic peptide effect with HS142-1, a GC-A receptor antagonist, CYP11B2 gene was significantly expressed. Also, exogenous natriuretic peptide suppressed the CYP11B2 gene expression, the dose of which was a commonly used concentration level in the treatment of heart failure. These results indicate that cardiac aldosterone synthesis is suppressed by NP and the balancing between aldosterone and NP would be very important in heart failure status.
As for pathophysiological roles of aldosterone, we recently found that aldosterone augments the ACE gene expression in neonatal rat cardiocytes, making a vicious cycle between tissue RAAS.
As mentioned above, we have studied about cardiac aldosterone synthesis and its pathophysiological significance in heart failure. In he renin-angiotensin-aldosterone system, not only angiotensin II but also aldosterone would provide unfavorable effects directly. The aspect of a paradigm shift has just been presented.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Yoshimura M, et al.: "Expression of aldosterone synthase gene in the failing human heart : quantitative analysis using modified real-time PCR"J Clin Endocrinol Metab. 87(8). 3936-3940 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ito T, et al.: "Inhibitory Effect of Natriuretic Peptides on Aldosterone Synthase Gene Expression in Cultured Neonatal Rat Cardiocytes"Circulation. 107. 807-810 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno Y, et al.: "Effect of perindopril on aldosterone production in the failing heart"Am J Cardiol. 89(10). 1197-1200 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto N, et al.: "Aldosterone is produced from ventricles in patients with essential hypertension"Hypertension. 39(5):. 958-962 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sakamoto T, et al.: "B-type natriuretic peptide after percutaneous transluminal septal myocardial ablation"Int J Cardiol. 83(2). 151-158 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mizuno Y, et al.: "Aldosterone Production is Activated in the Failing Ventricles in Humans"Circulation. 103(1). 72-77 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Mizuno, M. Yoshimura, H. Yasue, Y. Sakamoto, H. Ogawa, K. Kugiyama, E. Harada, M. Nakayama, S. Nakamura, T. Ito, Y. Saito & K. Nakao: "Aldosterone Production is Activated in the Failing Ventricles in Humans"Circulation. 103(1). 72-77 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] E. Harada, M. Yoshimura, H. Yasue, O. Nakagawa, M. Nakagawa, M. Harada, Y. Mizuno, M. Nakayama, Y. Shimasaki, T. Ito, S. Nakamura, K. Kuwahara, Y. Saito, K. Nakao & H. Ogawa: "Aldosterone Induces Angiotensin-Converting-Enzyme Gene Expression in Cultured Neonatal Rat Cardiocytes"Circulation. 104. 137-139 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yoshimura, H. Yasue & H. Ogawa: "Pathophysiological significance and clinical application of ANP and BNP in patients with heart failure"Can J Pharma Physiol. 79 (8). 730-735 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yoshimura, Y. Mizuno, M. Nakayama, T. Sakamoto, S. Sugiyama, H. Kawano, H. Soejima, N. Hirai, Y. Saito, K. Nakao & H. Yasue. Ogawa: "B-type natriuretic peptide as a sensitive marker of time- and dose-dependent effects of ACE inhibitor in patients with heart failure"Am J Med. 112(9). 716-720 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M. Yoshimura, S. Nakamura, T. Ito, M. Nakayama, E. Harada, Y. Mizuno, T. Sakamoto, Y. Yamamuro, Y. Saito, K. Nakao & H. Yasue. Ogawa: "Expression of aldosterone synthase gene in the failing human heart: quantitative analysis using modified real-time PCR"J Clin Endocrinol Metab. 87(8). 3936-3940 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Mizuno, H. Yasue, M. Yoshimura, H. Fujii, N. Yamamoto, M. Nakayama, E. Harada, T. Sakamoto, S. Nakamura, T. Ito, Y. Shimasaki, H. Ogawa, Y. Saito & K. Nakao: "Effect of perindopril on aldosterone production in the failing hear"Am J Cardiol. 89(10). 1197-1200 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N. Yamamoto, H. Yasue, Y. Mizuno, M. Yoshimura, H. Fujii, M. Nakayama, E. Harada, S. Nakamura, T. Ito & H. Ogawa: "Aldosterone is produce from ventricles in patients with essential hypertension"Hypertension. 39(5). 958-962 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Sakamoto, Y. Mizuno, H. Ogawa, M. Yoshimura, K. Kugiyama & H. Yasue: "B-type natriuretic peptide after percutaneous transluminal septal myocardial ablation"Int J Cardiol. 83(2). 151-158 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T. Ito, M. Yoshimura, S. Nakamura, M. Nakayama, Y. Shimasaki, E. Harada, Y. Mizuno, M. Yamamoto, M. Harada, Y. Saito, K. Nakao, H. Kurihara, H. Yasue & H. Ogawa: "Inhibitory Effect of Natriuretic Peptides on Aldosterone Synthase Gene Expression in Cultured Neonatal Rat Cardiocytes"Circulation. 107. 807-810 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yoshimura M, et al.: "Expression of aldosterone synthase gene in the failing human heart : quantitative analysis using modified real-time PCR"J Clin Endocrinol Mateb. 87(8). 3936-3940 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ito T, et al.: "Inhibitory Effect of Natriuretic Peptides on Aldosterone Synthase Gene Expression in Cultured Neonatal Rat Cardiocytes"Cirbulation 107 807-810 2003. 107. 807-810 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mizuno Y, et al.: "Angiotensin converting enzyme inhibits the production of aldosterone synthesis in patients with heart failure (accept後の校正中にて仮)"American Journal of Cardiology. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto, et al.: "Aldosterone is activated in the ventricles in patients with essential hypertension (accept後の校正中にて仮)"Hypertension. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yoshimura M, et al.: "B-type natriuretic peptide as a sensitive marker of time-and dose-dependent effects of ACE inhibitor in patients with heart failure"American Journal of Medicine. (In press).

    • Related Report
      2001 Annual Research Report
  • [Publications] 吉村道博 他: "Cardiac rennin-angiotensin-aldosterone系の新展開"心臓. 34(1). 58-60 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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