2001 Fiscal Year Final Research Report Summary
Possible involvement of facilitated aldose reductase activity in the accelerated vascular remodeling in rabbits with alloxan-induced hyperglycemia
| Project/Area Number |
12672209
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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 |
応用薬理学・医療系薬学
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
AZUMA Hiroshi Tokyo Medical & Dental University, Institute of Biomaterials & Bioengineering, Associate Professor, 生体材料工学研究所, 助教授 (20134736)
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| Co-Investigator(Kenkyū-buntansha) |
OBAYASHI Satoshi Tokyo Medical & Dental University, Faculty of Medicine, Associate Professor, 大学院・医歯学総合研究科, 助手 (10262180)
TSUJII Toshihiko Dokkyo University Medical School, Faculty of Medicine, Associate Professor, 医学部, 助教授 (90217307)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Aldose reductase / augmentation of intimal hvperplasia / endogenous NOS inhibitors / endothelin-1 / hvperglycemia / nitric oxide / polyol pathway / sorbitol |
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| Research Abstract |
Present experiments were designed to investigate whether or not the facilitation of polyol pathway is involved in the augmentation of intimal hyperplasia following endothelial denudation in rabbits with alloxan-induced hyperglycemia Twelve weeks after a single bolus injection of alloxan or saline, rabbits underwent unilateral endothelial denudation of the carotid artery to cause intimal hyperplasia. An intimal hyperplasia was caused 4 weeks after the denudation and significant augmentation of the intimal hyperplasia was brought about under the hyperglycemia. The augmentation of intimal hyperplasia was accompanied by the accelerated accumulation of endogenous NOS inhibitors in regenerated endothelial cells, accelerated impairment of NO production and acceleratedaccumulation of ET-1 within the vessel wall. Sorbitol levels in aortic endothelial cells and within the vessel wall were significantly increased with hyperglycemia. All these changes which had been brought abdlit by the hyperglycemia were effectively improved by the administration offidarestat as a selective aldose reductase inhibitor for 5 weeks from 1 week before to 4 weeks after the denudation. These findings suggest that facilitation of polyol pathway possibly plays an important role for the augmentation of intimal hyperplasia with hyperglycemia.
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