| Project/Area Number |
08457212
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
EGASHIRA Kensuke KYUSHU UNIVERSITY FACULTY OF MEDICINE,ASSISTANT PROFESSOR, 医学部, 講師 (60260379)
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| Co-Investigator(Kenkyū-buntansha) |
SUEISHI Katsuo KYUSHU UNIVERSITY,Faculty of MEdicine, Proffessor, 医学部, 教授 (70108710)
ICHIKI Toshihiro KYUSHU UNIVERSITY,Faculty of Medicine, Reseach Felow, 医学部, 医員
OHARA Yuichi KYUSHU UNIVERSITY,Faculty of Medicine, Assistant Professor, 医学部, 助手 (90185364)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1996: ¥4,300,000 (Direct Cost: ¥4,300,000)
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| Keywords | nitric oxide / angiotensin-converting enzyme / angiotensin II / thrombosis / atherosclerosis / oxidative stress / macrophages / アンジオテンシンII受容体 / 血管リモデリング / 内皮細胞 / 狭心症 / レニン-アンギオテンシン系 / アンギオテンシン変換酵素 |
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| Research Abstract |
We have recently showed that chronic inhibition of nitric oxide (NO) synthesis by Nomega-nitoro-L-arginine methy ester (L-NAME) induces a marked monocyte infiltration and monocyte chemoattractant protein-1 (MCP-1) expression in rat hearts. However, the mechanisms of these changes are not known. The migration of monocytes into the blood vessels is a critical early event leading to atherosclrosis and MCP-1 is a major chemokine for monocytes. Nuclear factor-KB (NF-kappaB) is believed to be an important transcriptional factor that induces inflammatory cytokines such as MCP-1. Angiotensin II has been shown to activate chemotaxis and NF-kappaB in vitro.
In the present study, we tested the hypothesis that angiotesin II mediates such inflammatory changes and NF-kappaB activation in rat hearts induced by inhibition of NO synthesis. We observed a marked increases in monocyte infiltrarion into coronary vessels and myocardial interstitial areas, MCP-1 expression and NF-kappaB activity during on the 3rd day of L-NAME administation. Along eith these changes, vascular superoxide anion production is also increased. Treatment with an angiotensin II type 1 receotor antagonist prevented all of these changes induced by L-NAME administration.
Our present results sugest that endogenous angiotensin II pleays an important role in mediating inflammatory changes in this model and that okidative stress, NF-kappaB activation and MCP-1 expression may be involved in the pathogenesis of the inflammation. Results also suggest that angiotenisin II receptor blockade may have beneficial effects in early arteriosclerosis and/or atheroscleorsis.
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