1998 Fiscal Year Final Research Report Summary
THE REGULATION OF ENDOTHELIAL CONSTITUTIVE NITRIC OXIDE SYNTHASE IN REGENERATED ENDOTHLIAL CELLS
| Project/Area Number |
08670802
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
OHARA Yuichi KYUSHU UNIVERSITY,DEPARTMENT OF ANGIOLOGY AND CARDIOVASCULAR CLINIC,ASSISTANT PROFESSOR, 医学部, 助手 (90185364)
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| 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)
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| Project Period (FY) |
1996 – 1998
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| Keywords | LUCIGENIN / SEROTONIN / ENDOTHELIUM DEPENDENT VASODILATION / ENDOTHELIUM DERIVED NITRIC OXIDE / xanthine dehydrogenase |
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| 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.
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