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1998 Fiscal Year Final Research Report Summary

THE REGULATION OF ENDOTHELIAL CONSTITUTIVE NITRIC OXIDE SYNTHASE IN REGENERATED ENDOTHLIAL CELLS

Research Project

Project/Area Number 08670802
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

Principal Investigator

OHARA Yuichi  KYUSHU UNIVERSITY,DEPARTMENT OF ANGIOLOGY AND CARDIOVASCULAR CLINIC,ASSISTANT PROFESSOR, 医学部, 助手 (90185364)

Co-Investigator(Kenkyū-buntansha) SHIMOKAWA Hiroaki  KYUSHU UNIVERSITY,DEPARTMENT OF ANGIOLOGY AND CARDIOVASCULAR CLINIC,ASSIOCIATE P, 医学部, 助教授 (00235681)
EGASHIRA Kensuke  KYUSHU UNIVERSITY,DEPARTMENT OF ANGIOLOGY AND CARDIOVASCULAR CLINIC,ASSISTANT PR, 医学部, 講師 (60260379)
Project Period (FY) 1996 – 1998
KeywordsLUCIGENIN / SEROTONIN / ENDOTHELIUM DEPENDENT VASODILATION / ENDOTHELIUM DERIVED NITRIC OXIDE / xanthine dehydrogenase
Research Abstract

We tested the hypothesis that accelerated degradation of endothelium-derived nitric oxide by superoxide anion in regenerated endothelium after baloon denudation. To measure superoxide anion production within normal pig coronary arteries (control vessels) and coronary arteries two weeks after baloon dunudation (injured vessels), we used an assay for superoxide anion based on the chemiluminescence of lucigenin using luminometer (Shimazu). In pathological studies, moderate intimal thickening was observed in injured vessels. In separate isometric tension studies, serotonin- induced vasoconstriction was markedly augmented in injured vessel segments. Injured vessels produced two to threefold more superoxide anion than control vessels (n = 8). Interestingly, there was no difference between denuded control vessels and denuded injured vessels, suggesting that the regenerated endothlium is a source of superoxide anion production. To further investigate the molecular mechanisms of excess production of superoxide anion within regenerated endothlium, we excised injured coronary vessels and quantitated the expression of enzyme by immunohistochemical method using monoclonal antibody against mouse endothelial constitutive nitric oxide synthase (ecNOS), mouse Cu-Zn containing superoxide dismutase (Cu-Zn SOD), and mouse xanthine dehydrogenase (XDH). We observed ecNOS expression was significantly attenuated within regenerated endothlium, whereas either Cu-Zn SOD or XDH expression unchanged. Increased endothelial superoxide anion production and attenuated expression of ecNOS within regenerated endothlium after baloon denudation may play an important role in the early atherosclerotic process.

  • Research Products

    (7 results)

All Other

All Publications (7 results)

  • [Publications] Ohara Y et al: "Probucol improves endothelial-dependent relaxation and decreases vascular superoxide production in choelesterol-fed rabbits." American Journal of the Medical Sciences. 315. 242-247 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara Y et al: "Early induction of transforming growth factor-beta via angiotensin II type I receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis." Hypertension. 32. 273-279 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohara Y.et al: "Regulation of expression of the endothelial cell nitric oxide synthase" Clinical & Experimental Pharmacology & Physiology. 23. 251-255 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara Y.et al: "Modulation of endothelial cell nitric oxide synthase expression" Japanese Circulation Journal. 60. 815-821 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohara Y.et al: "Central role of vascular smooth muscle hyperreactivity in coronary hyperconstriction after balloon injury in miniature pigs" Coronary Artery Disease. 8. 69-75 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Inoue N,Ohara Y et al: "Probucol improves endothelial-dependent relaxation and decreases vascular superoxide production in choelesterol-fed rabbits" American Journal of the Medical Sciences. 315. 242-247 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tomita H,Egashira K,Ohara Y et al: "Early induction of transforming growth factor-beta via angiotensin II type i receptors contributes to cardiac fibrosis induced by long-term blockade of nitric oxide synthesis in rats" Hypertension. 32. 273-239 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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