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VASOMOTOR-ACTIVE FACTORS DERIVED FROM ENDOTHELIALCELLS IN MICE ARTERIES.

源自小鼠动脉内皮细胞的血管舒缩活性因子。

基本信息

批准号：
10470020
负责人：
KANNO Morio
金额：
$ 0.77万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

There is enough evidence indicating that biologically active substances released from the endothelial cells of blood vessels play physiologically and/or pathophysiologically important roles in regulating thrombogenesis or development of atherosclerosis. Especially, balance of endothelium-derived constricting factors(EDCF) and endothelium-derived relaxing factors(EDRF) is very important. We found that EDHF(endothelium-derived hyperpolarizing faetor) , one of EDRF, regulates actively vasomotor tone of smaller arteries less than 300 mm in diameter in rats, and hyperpolarization which EDHF produces in arterial smooth muscle cells by activating apamin-and charibdotoxin-sensitive KィイD1+ィエD1 channels decreases CaィイD12+ィエD1 sensitivity of contractile elements as well as inhibiting CaィイD12+ィエD1 influx through L-type CaィイD12+ィエD1 channels. We also found that EDHF plays an essential role in maintaining endothelial function regulating vasomotor tone of arteries as a backup system to EDNO in female rats. In order to clarify more the physiological or pathophysiological significance of EDHF and its molecular mechanism, more sophisticated studies such as those using transgenic mice are required in near future. We found that Microvessel Perfusion System is adequate experimental methods observing changes in vasomotor tone of very small arteries obtained from small animals such as mice.

有足够的证据表明，从血管内皮细胞释放的生物活性物质在调节血栓形成或动脉粥样硬化的发展中发挥重要的生理和/或病理生理作用。其中，内皮源性收缩因子（EDCF）和内皮源性舒张因子（EDRF）的平衡尤为重要。我们发现EDHF内皮源性超极化因子（endothelium-derived hyperpolarizing favorites）是EDRF的一种，在大鼠中主动调节直径小于300 mm的小动脉的血管张力，EDHF通过激活apamin和apbdotoxin敏感的K + D1通道在动脉平滑肌细胞中产生超极化，降低收缩元件的Ca + D12+通道D1敏感性，并抑制Ca + D12+通道。钙离子D1通过L型钙离子D12+钙离子D1通道内流。我们还发现，EDHF在维持内皮功能中起着重要作用，调节动脉血管张力，作为EDNO的后备系统。为了进一步阐明EDHF的生理或病理生理学意义及其分子机制，在不久的将来需要更复杂的研究，例如使用转基因小鼠的研究。我们发现，微血管灌注系统是观察小动物（如小鼠）微小动脉血管张力变化的适当实验方法。