| Project/Area Number |
20590888
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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 | Tokai University |
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Principal Investigator |
ISHIDA Hideyuki Tokai University, 医学部, 教授 (20222424)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 血栓 / 血管内皮細胞 / 活性酸素種 / in vivo / 活性酸素 / ミトコンドリア |
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| Research Abstract |
Although nicorandil has a number of beneficial cardiovascular actions, its effects on endothelial cells in the context of thrombosis have not been elucidated. Therefore, we have examined that antithrombotic action by protection of vascular endothelial cells using nicorandil
Arterial thrombosis was induced by endothelial injury caused by FeCl_3 in the mouse testicular artery. Thrombus growth led to complete occlusion 12 min after endothelial injury in control mice. The antiplatelet agent, nicorandil significantly slowed the growth of thrombi, resulting in arterial occlusion after 55 min. In the absence of endothelial cells, nicorandil did not inhibit platelet aggregation. The beneficial effect of nicorandil was prevented by 5-hydroxydecanoate, but not by L-NAME. The production of reactive oxygen species by FeCl3 treatment was measured with the specific fluorescent probe, dihydrorhodamine 123. After FeCl3 treatment, nicorandil significantly inhibited the increase in fluorescence. In further experiments, incubation of human umbilical vein endothelial cells with nicorandil did not change the endothelial nitric oxide synthase (eNOS) mRNA levels, eNOS phosphorylation or nitrite production.
Nicorandil attenuates FeCl_3-induced thrombus formation in the mouse testicular artery, which suggests that it may inhibit the generation of reactive oxygen species by FeCl_3-treated endothelial cells through activation of the mitochondrial ATP-sensitive potassium channels.
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