EET homologs potently dilate coronary microvessels and activate BK(Ca) channels.
EET homologs potently dilate coronary microvessels and activate BK(Ca) channels.
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DOI：
10.1152/ajpheart.2001.280.6.h2430
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发表时间：
2001-06
期刊：
影响因子：
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通讯作者：
Yongde Zhang;C. Oltman;T. Lu;Hon-Chi Lee;K. Dellsperger;M. Vanrollins
中科院分区：
文献类型：
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作者：
Yongde Zhang;C. Oltman;T. Lu;Hon-Chi Lee;K. Dellsperger;M. Vanrollins
环氧二十碳三烯酸（Epoxyeicosatrienoic acids，EAE）由内皮细胞释放，通过超极化血管肌细胞有效扩张小动脉。在本研究中，我们研究了Escherichia coli在扩张犬和猪冠状动脉微血管（50-140 microm ID）和激活大电导Ca 2+激活的K+（BK（Ca））通道中的结构特异性。将EET区域异构体和对映异构体的效力和功效与两种EET同系物的效力和功效进行比较：环氧二十碳四烯酸（EEQs），其由二十碳五烯酸通过相同的细胞色素P-450环氧加氧酶从花生四烯酸产生E3，和环氧二十二碳四烯酸（EDTs），其是两个碳更长的E3。EC 50值为3-120 pM，但无区域或立体选择性，Eclamping有效扩张犬和猪微血管。令人惊讶的是，EEQ和EDT在扩张微血管方面具有相当的效力和功效。此外，50 nM 13，14-EDT激活BK（Ca）通道的功效与50 nM 11，12-EET对映体相同。我们的结论是，冠状动脉微血管和BK（Ca）通道具有低的结构特异性，EQUs和EDTs，从而也可能是内皮源性超极化因子。
Epoxyeicosatrienoic acids (EETs) are released from endothelial cells and potently dilate small arteries by hyperpolarizing vascular myocytes. In the present study, we investigated the structural specificity of EETs in dilating canine and porcine coronary microvessels (50-140 microm ID) and activating large-conductance Ca2+-activated K+ (BK(Ca)) channels. The potencies and efficacies of EET regioisomers and enantiomers were compared with those of two EET homologs: epoxyeicosaquatraenoic acids (EEQs), which are made from eicosapentaenoic acid by the same cytochrome P-450 epoxygenase that generates EETs from arachidonic acid, and epoxydocosatetraenoic acids (EDTs), which are EETs that are two carbons longer. With EC50 values of 3-120 pM but without regio- or stereoselectivity, EETs potently dilated canine and porcine microvessels. Surprisingly, the EEQs and EDTs had comparable potencies and efficacies in dilating microvessels. Moreover, 50 nM 13,14-EDT activated the BK(Ca) channels with the same efficacy as either 11,12-EET enantiomer at 50 nM. We conclude that coronary microvessels and BK(Ca) channels possess low structural specificity for EETs and suggest that EEQs and EDTs may thereby also be endothelium-derived hyperpolarizing factors.