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Treatment and prevention of microvascular disorders

Research Project

Project/Area Number 07557346
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

EGASHIRA Kensuke  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (60260379)

Co-Investigator(Kenkyū-buntansha) TSUTSUI Hiroyuki  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (70264017)
MOHRI Masahiro  KYUSHU UNIVERSITY,FACULTY OF MEDICINE,ASSOCIATE PROFESSOR, 医学部, 講師 (60264032)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsangina pectoris / nitric oxide / endothelial cells / coronary circulation / serotonin / angiotensin-converting enzyme inhibitor / angiotensin receptors / 血管病変 / 心筋虚血 / 病理学
Research Abstract

We have created animal models of microvascular disorders. Long-term inhibition of nitric oxide synthase with administering chronically an nitric oxide inhibitor (N^<omega>-nitro-L-arginine methyl ester, L-NAME) to rats and pigs caused coronary vascular structural changes (medial thickening and perivascular fibrosis). We examined whether microvascular responses to serotonin is altered in the pig model. After anesthesia, we infused serotonin into the coronary artery and found that the drug significantly decreased coronary blood flow in the L-NAME treated pigs but not in the control pigs. the vasomotor respons to serotonin was similar between the two groups. Thus, these data suggest that the enhanced decrease in coronary blood flow to serotonin was due to augmented constriction of microvessels.
We aimed to provoke myocardial ischemia in the pig model. We administered papaverine into the coronary artery and found that the drug induced myocardial ischemia (myocardial lactate production). Because the papaverine-induced myocardial ischemia was associated with increased coronary blood flow, we concluded that the papaverine-induced myocardial ischemia was caused by altered distribution of regional myocardial blood flow. We also examined whether addition of angiotensin II receptor antagonists ameliorate the development of structural changes in coronary microvessels and thus reduce papaverine-induced myocardial ischemia. We found that the angiotensin II type 1 receptor antagonists prevented both the development of microvascular structural changes and papaverine-induced myocardial ischemia.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Numaguchi K et al: "Chronic inhibition of nitric oxide synthesis causes.." Hypertension. 26. 957-962 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Itoh A et al: "Chronic inhibition of endothelium-derived nitric oxide." Circulation. 92. 2636-2644 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kadokami T et al: "Altered serotonin receptor subtypes mediate coronary.." Circulation. 94. 182-189 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K et al: "Effects of L-arginine on endothelium-dependent..." Circulation. 94. 130-134 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K Hirooka Y Kai H Sugimachi M Suzuki S Inou T Takeshita A.: "Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasodilation in patients with hypercholesterolemia." Circulation. 89. 2519-2524 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K Suzuki S Hirooka Y Kai H Sugimachi M Imaizumi T Takeshita A.: "Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P." Hypertension. 25. 201-206 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kuga T Egashira K Mohri M Tsutsui H Harasawa Y Urabe Y Ando S Shimokawa H Takeshita A.: "Bradykinin-induced vasodilation is impaired at the atherosclerotic site but is preserved at the spastic site of human coronary arteries in vivo." Circulation. 92. 183-189 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katsuda Y Egashira K Akatsuka Y Narishige T Shimokawa H Takeshita A.: "Endothelium-derived nitric oxide does not modulate metabolic coronary vasodilation induced b tachycardia in dogs." J Cardiovasc Pharmac. 26. 437-444 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Ito A Egashira K Kadokami T Fukumoto Y Takayanagi T Nakaike R Kuga T Sueishi K Shimokawa H Takeshita A.: "Chronic inhibition of endothelium-derived nitric oxide synthesis causes coronary microvascular structural changes and hyperreactivity to serotonin in pigs." Circulation. 92. 2636-2644 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Numaguchi K Egashira K Takemoto M Kadokami T Shimokawa H Sueishi K Takeshita A.: "Chronic inhibition of nitric oxide synthesis causes pathologic coronary remodeling and myocardial fibrosis." Hypertension. 26. 957-962 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K Katsuda Y Mohri M Kuga T Tagawa T Shimokawa H Takeshita A.: "Basal release of endothelium-derived nitric oxide at the spastic site in patients with variant angina." J Am Coll Cardiol. 27. 1444-1449 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K Hirooka Y Mohri M Kuga T Takeshita A.: "Effects of L-arginine supplementation on endothelium-dependent coronary vasodilation induced by acetylcholine in patients with angina and normal coronary arteriograms." Circulation. 94. 130-134 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Kadokami T Egashira K Kuwata K Fukumoto Y Kozai T Yasutake H Kuga T H Sueishi K Takeshita A.: "Altered serotonin receptor subtypes mediate coronary microvascular hyperreactivity in pigs with chronic inhibition of nitric oxide synthesis." Circulation. 94. 182-189 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Egashira K Katsuda Y Mohri M Kuga T Tagawa T Kubota T Hirakawa Y Takeshita A.: "The role of endothelium-derived nitric oxide in coronary vasodilatation induced by pacing tachycardia in humans." Cir Res. 79. 331-335 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Takemoto M Egashira K Usui M Numaguchi K Tomita H Tsutsui H Shimokawa H Sueishi K Takeshita A.: "Important role of tissue angiotensin-converting enzyme activity in the pathogenesis of coronary vascular and myocardial structural changes induced by long-term blockade of nitric oxide synthesis in rats." J Clin Invest. 99. 278-287 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Numaguchi K et al: "Chronic inhibition of nitric oxide synthesis causes.." Hypertension. 26. 957-962 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Itoh A et al: "Chronic inhibition of endothelium-derived nitric oxide." Circulation. 92. 2636-2644 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kadokami T et al: "Altered serotonin receptor subtypes mediate coronary.." Circulation. 94. 182-189 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Egashira K et al: "Effects of L-arginine on endothelium-dependent..." Circulation. 94. 130-134 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Numaguchi K.et al.: "Chronic inhibition of nitric oxide synthesis causes coronary microvascular remodeling in rats" Hypertension. 26part 1. 957-962 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Itoh A.et al: "Chronic.inhibition of endothelium-derived nitric oxide synthesis causes coronary microvascular structural changes and hyperreactivity to serotonin in pigs" Circulation. 92. 2636-2644 (1995)

    • Related Report
      1995 Annual Research Report

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

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