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The endothelium-derived hyperpolarizing factor (EDHF) to maintain vascular tone actually exists

维持血管张力的内皮源性超极化因子（EDHF）确实存在

基本信息

批准号：
16590210
负责人：
KAGOTA Satomi
金额：
$ 1.86万
依托单位：
Mukogawa Women's University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

Vascular endothelial cells synthesize and release various vasorelaxing factors, including nitric oxide (NO) and an endothelium-derived hyperpolarizing factor (EDHF), which regulate the tonus of underlying smooth muscle cells. It is now widely accepted that EDHF, together with NO, is associated with regulation of the vascular caliber in small arteries. However, there is not yet universal agreement on the nature of EDHF, the cellular processes that mediate EDHF-mediated hyperpolarization, or its physiological and pathophysiological significance. Thus, as a first step, the present study attempted to establish a real-time analysis for measurement of EDHF-mediated hyperpolarization and relaxation in vascular smooth muscle cells. Changes of the smooth muscle cell membrane potential and contraction-relaxation response were coincidentally determined using confocal fluorescence microscopy. The findings were used to examine the characteristics of the EDHF-mediated response in mesenteric arteries of SHR/NDmcr-cp (SHR-cp) rats, a rat model of metabolic syndrome.To measure the smooth muscle cell membrane potential induced by acetylcholine in rat mesenteric arteries, they were visualized using a membrane potential-sensitive fluorescence dye, DiBAC_4. The distance between wires inserted into a vessel was determined using the NIH image as a vasorelaxation response. We found that acetylcholine induced sustained and stable hyperpolarization in the presence of nitro-L-arginine methyl ester, an inhibitor of NO synthase. Furthermore, EDHF-mediated hyperpolarization and vasorelaxation in mesenteric arteries of SHR-cp rats were reduced compared with those of Wistar-Kyoto rats. In contrast, NO-mediated relaxation was increased in SHR-cp rats. These findings suggest that impairment of the EDHF-mediated response occurs in metabolic syndrome, and that the possibility of a back-up mechanism between NO and EDHF has important pathophysiological implications.

血管内皮细胞合成和释放各种血管松弛因子，包括一氧化氮(NO)和内皮衍生超极化因子(EDHF)，它们调节底层平滑肌细胞的张力。现在人们普遍认为，EDHF和NO一起与小动脉的血管管径调节有关。然而，对于EDHF的性质、介导EDHF介导的超极化的细胞过程或其生理和病理生理学意义，目前还没有普遍的共识。因此，作为第一步，本研究试图建立一种实时分析方法来测量EDHF介导的血管平滑肌细胞的超极化和松弛。用共聚焦荧光显微镜同时测定平滑肌细胞膜电位和收缩-松弛反应的变化。为研究代谢综合征大鼠模型SHR/NDmcr-cp(SHR-cp)肠系膜动脉EDHF介导的反应特征，采用膜电位敏感型荧光染料DiBAC_4对乙酰胆碱诱导的大鼠肠系膜动脉平滑肌细胞膜电位进行了观察，并用NIH图像确定了插入血管的导线之间的距离作为血管松弛反应。我们发现，在一氧化氮合酶抑制剂--硝基-L-精氨酸甲酯存在下，乙酰胆碱可诱发持续稳定的超极化。此外，SHR-cp大鼠肠系膜动脉EDHF介导的超极化和血管舒张性较Wistar-京都大鼠明显减弱。相反，SHR-cp大鼠的NO介导的松弛作用增强。这些发现提示代谢综合征患者存在EDHF介导的反应障碍，NO和EDHF之间可能存在一种后备机制具有重要的病理生理学意义。