Project/Area Number |
10670625
|
Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Circulatory organs internal medicine
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Research Institution | TOHOKU UNIVERSITY |
Principal Investigator |
KOMARU Tatsuya Department of Cardiovascular Medicine, Graduate School of Medicine, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (30261530)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
Keywords | coronary microvessels / myocardial ischemia / hypercholesterolemia / vasodilation / pertussis toxin-sensitive G protein / biological signal transduction / biological defence system / cross talk between myocardium and microvessels / 冠循環 / 微小動脈 / G蛋白 / ATP感受性K^+チャネル / 百日咳毒素 |
Research Abstract |
The purpose of the present study were to detect the vasodilatory signals which are transduced to coronary microvessels from the ischemic myocardium, to elucidate the pathway of the signal transduction and to elucidate whether the signal transduction is impaired im hypercholesterolemia. To detect the vasoactive signal from the ischemic heart, coronary microvessels (100 - 300 μm in diameter, pressurized with 60 cmHィイD22ィエD2O, stop flow condition) were isolated from rabbits and gently layed on the canine beating heart. After establishment of the intrinsic tone of the isolated microvessels, myocardial ischemia of the canine beating heart was induced by coronary occlusion, and the diameter changes of those isolated microvessels were measured with intravital microscope equipped with a floating objective. The isolated microvessels began to dilate in 2 minutes after the onset of ischemia, the peak dilation took place in 5 minutes and the dilation persisted for 10 minutes. The dilation was abol
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ished by pertussis toxin and partially inhibited by glibenclamide indicating that GィイD2iィエD2 protein and KィイD2ATPィエD2 channels are involved in the vasodilatory signal transduction. To investigate the impact of hypercholesterolemia on this vasomotion, we divided rabbits into hypercholesterolemic (HC) and normocholesterolemic (NC) rabbits, and the microvascular responses to myocardial ischemia were compared using the abovementioned method. In this protocol, microvessels were precontracted with U46619 (thromboxane analogue). There was no significant difference in the magnitude of dilation in response to myocardial ischemia between HC and NC rabbits. Nitroprusside further dilated those microvessels in both groups. The dilation of microvessels from NC rabbits were significantly less than that of microvessels in which U46619 was not applied. Thus, it is possible that U46619 nonspecifically blunted the microvascular dilation in both groups. Similar protocol should be done without using U46619 before concluding on the impact of hypercholesterolemia on cross talk between ischemic myocardium and the coronary microvessels. Less
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