| Project/Area Number |
11670672
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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 | Nagoya University |
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Principal Investigator |
HAYASHI Toshio School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (80303634)
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| Co-Investigator(Kenkyū-buntansha) |
KUMAGAI Yoshito Isukuba University, School of Medicine, Associate Professor, 医学部, 助教授 (00250100)
IGUCHI Akihisa School of Medicine, Nagoya University, Professor Associate, 医学部, 教授 (20109763)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Nitric Oxide / Atherosclerosis / Citrolline-Arginine cycle / regression / super oxide anion / arginase / NADPHオキシダーゼ / 糖尿病 / 誘導型NO合成酵素(iNOS) / 活性酸素(O_2) / 高脂血症 / 加齢 |
|---|
| Research Abstract |
We tried to use vascular endocrinological system (citrulline-arginine cycle) for therapy of advanced atherosclerosis. We also tried to investigate the role of inducible nitric oxide synthase (iNOS) and soluble guanylate cyclase in aged advanced atherosclerotic animal model. Firstly, we observed iNOS and ONOO^- in T cell and macrophages in rabbit advanced atherosclerosis. Application of L-arginine but not citrulline retards progression of atherosclerosis. Secondly, we determined dothelial and non-endothelial vascular responses, eNOS and soluble guanylate cyclase (sGC) using rats model. Hyperglycemia was induced by intraperitoneal injection of streptozotocin in young (9wks), middle aged (54wks) and elderly (108 wks) male wister rats. After 1 to 12 weeks of hyperglycemia induction, rats were sacrificed and NO related responses and molecular analyses were investigated in thoracic aortas. The fasting blood glucose was increased 340±13 mg/dl in hyperglycemic induced rats. NO stimulated and basal responses were not significantly changed in younger (9wks.) rats when they were slightly decreased under hyperglycemia for more than 9 weeks. Endothelium independent response by nitroglycerin was diminished in elderly rats (108 wks) as compared with those in younger and middle aged rats (54 wks). Further, it was diminished in status of hyperglycemia for longer than 4 weeks. NO stimulated and basal responses were slightly decreased in aortas of elderly rats, and significantly decreased in hyperglycemia and depending on the duration of hyperglycemia. eNOS and soluble guanylate cyclase protein tended to decrease in aged diabetic rats. Further, O_2^- was increased by aging and hyperglycemia.
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