| Project/Area Number |
09672244
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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 |
Biological pharmacy
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| Research Institution | Health Sciences University of Hokkaido |
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Principal Investigator |
HIRAFUJI Masahiko Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, 薬学部, 助教授 (20142987)
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| Co-Investigator(Kenkyū-buntansha) |
HAMAUE Naoya Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido Instr, 薬学部, 助手 (70221504)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | docosahexaenoic acid / vascular smooth muscle cells / intracellular calcium / nitric oxide / calcium channels / 5-hydroxytryptamine / angiotensin II / 高血圧症 / ラット / 血管内皮細胞 |
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| Research Abstract |
The aim of the present project was to investigate the effects of docosahexaenoic acids (DHA) on vascular cells functions, using cultured aortic smooth muscle cells. Treatment of rat aortic smooth muscle cells with DHA in culture had no significant effect on the cell growth rate and cell hypertrophy induced by angiotensin II.The effects of DHA on intracellular C^<2+> dynamics and nitric oxide (NO) production were also examined using cells isolated from stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar Kyoto rats (WKY). The resting and peak concentrations of intracellular C^<2+> were significantly higher in cells from SHRSP than in WKY stimulated with angiotensin II or 5-hydroxytryptamine (5-HT). DHA treatment significantly suppressed the intracellular C^<2+> dynamics induced by angiotensin II and 5-HT in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. It was suggested that DHA inhibited C^<2+> influx through the voltage-dependent o
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r 2nd messenger-operated C^<2+> channels, but not store-operated channels. The total NO production induced by interleukin-1beta (IL-1beta) was significantly lower in cells from SHRSP than from WKY.DI-LA treatment significantly increased IL-l3b-induced NO production in cells from WKY, while the cells from SHRSP were refractory to DHA treatment. The increase in NO production was due to the stimulation of inducible NO synthase protein induction, as analyzed by Western bloffing method. It is also suggested that DHA treatment can prevent cell damage evoked by IL-lbeta-induced NO.These studies suggest that the altered intracellular C^<2+> dynamics induced by contractile agonists and the diminished NO production in vascular smooth muscle cells play a role in the pathophysiology of SHRSP.Since the intracellular Ca and NO plays an important role in vascular smooth muscle cell functions, the properties to improve these functions can be contributed to the beneficial effect of DHA on cardiovascular disorders. Less
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