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Pathogenesis and molecular mechanisms of coronary circulatory dysfunction in congestive heart failure

Research Project

Project/Area Number 08670805
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY FACULTY OF MEDICINE

Principal Investigator

MOHRI Masahiro  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 助手 (60264032)

Co-Investigator(Kenkyū-buntansha) ICHIKI Toshihiro  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,RESEARCH FELLOW, 医学部, 非常勤研究員
OHARA Yuichi  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 助手 (90185364)
EGASHIRA Kensuke  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (60260379)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordscongestive heart failure / coronary circulation / endothelium / nitric oxide / substance-P / bradykinin / oxygen radical
Research Abstract

The aims of the present investigations were to elucidate the pathogenesis and the mechanisms of coronary circulatory dysfunction in congestive heart failure. We have focused on endogenous vasoactive substances derived from the vascular endothelium and related substrates and drugs, and performed the following studies in an animal model of as well as in patients with congestive heart failure.
First, we have developed a conscious canine model of congestive heart failure in which ventricular tachypacing was performed for 4 to 6 weeks using a surgically implanted pacing catheter. This model is characterized by depressed systolic and diastolic ventricular function and systemic neurohumoral alterations that resembled human congestive heart failure. In this model, we found that ATP-sensitive potassium channels of the coronary circulation exerted greater contribution to myocardial perfusion in dogs with heart failure as compared with those with normal LV function. Furthermore, coronary vascular … More free radical generation was increased through an activation of coronary endothelial xanthine oxidase. The control of coronary blood flow in response to metabolic stimuli was also examined. The contribution of endothelium-derived nitric oxide (EDNO) to the metabolic coronary microvascular dilation was augmented in heart failure.
Second, the role of EDNO in regulating coronary blood flow in response to endogenous vasoactive peptides, bradykinin (BK) and substance-P (SP) was examined in awake patients. Both agonists dilated coronary arteries and arterioles via EDNO-dependent mechanism. Angiotensin-converting enzyme inhibitor (ACEI) acutely augmented dilator response of BK in patients, suggesting that ACEI may exert its beneficial effects on the clinical outcome by ameliorating myocardial perfusion. Finally, we studied the functional role of EDNO in regulating coronary blood flow in patients with heart failure by testing the effects of L-arginine analog, LNMMA given in the coronary circulation. We found that constrictor effect of LNMMA was blunted in heart failure, therefore suggesting that basal release of EDNO is decreased in the coronary circulation in patients with heart failure. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Mohri M, et al.: "Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure." Hypertension. 30. 50-56 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tagawa T, Mohri M, et al.: "Role of nitric oxide in substance P-induced vasodilation differs between the coronary and forearm circulation in humans." J Cardiovasc Pharmacol. 29. 546-553 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuga T, Mohri M, et al.: "Bradykinin-induced vasodilation of human coronary arteries in vivo:role of nitric oxide and angiotensin-converting enzyme" J Am Coll Cardiol. 30. 108-112 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Egashira K, Mohri M, et al.: "The role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing thchycardia in humans." Circ Res. 79. 331-335 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tada H, et al.: "Role of endothelium-derived nitric oxide in metabolic coronary vasodilation in dogs with pacing-induced heart failure." Circulation. 8(suppl I). I-304 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 毛利 正博, 竹下 彰: "心肥大・心不全に伴う微小冠循環異常" Cardiac Practice. 8. 217-221 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mohri M,et al.: "Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure." Hypertension. 30. 50-56 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tagawa T,Mohri M,et al.: "Role of nitric oxide in substance P-induced vasodilation differs between the coronary and forearm circulation in humans." J Cardiovasc Pharmacol. 29. 546-553 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kuga T,Mohri M,et al.: "Bradykinin-induced vasodilation of human coronary arteries in vivo : role of nitric oxide and angiotensin-converting enzyme" J Am Coll Cardiol. 30. 108-112 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Egashira K,Mohri M,et al.: "The role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans." Circ Res. 79. 331-335 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Tada H,et al.: "Role of endothelium-derived nitric oxide in metabolic coronary-vasodilation in dogs with pacing-induced heart failure." Circulation. 8(suppl I). I-304 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mohri M,et al.: "Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure." Hypertension. 30. 50-56 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tagawa T,Mohri M,et al.: "Role of nitric oxide in substance P-induced vasodilation differs between the coronary and forearm circulation in humans." J Cardiovasc Pharmacol. 29. 546-553 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Kuga T,Mohri M,et al.: "Bradykinin-induced vasodilation of human coronary arteriesin vivo:role of nitric oxide and angiotens in-converting enzyme" J Am Coll Cardiol. 30. 108-112 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Egashira K,Mohri M,et al.: "The role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans." Circ Res. 79. 331-335 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tada H,et al.: "Role of endothelium-derived nitric oxide in metabolic coronary vasodilation in dogs with pacing-induced heart failure." Circulation. 8(suppl I). I-304 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 毛利正博、竹下 彰: "心肥大・心不全に伴う微小冠循環異常" Cardiac Practice. 8. 217-221 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mohri M,et al.: "Basal release of nitric oxide is decreased in the coronary circulation in patients with heart failure." Hypertension. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Tada H,et al.: "Role of endothelium-derived nitric oxide in metabolic coronary vasodilation in dogs with pacing-induced heart failure." Circulation. 8(suppl I). I-304 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tagawa T,Mohri M,et al.: "Role of nitric oxide in substance P-induced vasodilation differs between the coronary and forearm circulation in humans." J Cardiovasc Pharmacol. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 毛利正博、竹下 彰: "心肥大・心不全に伴う微小冠循環異常" Cardiac Practice. (印刷中).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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