MECHANISM OF ACTION OF CEREBRAL EPOXYEICOSATRIENOIC ACIDS ON CEREBRAL ARTERIAL SMOOTH-MUSCLE
MECHANISM OF ACTION OF CEREBRAL EPOXYEICOSATRIENOIC ACIDS ON CEREBRAL ARTERIAL SMOOTH-MUSCLE
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DOI：
10.1152/ajpheart.1992.263.2.h519
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发表时间：
1992-08-01
影响因子：
--
通讯作者：
HARDER, DR
中科院分区：
文献类型：
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作者：
GEBREMEDHIN, D;MA, YH;HARDER, DR
用[C-14]花生四烯酸孵育猫脑的微粒体制备物，产生环氧二十碳三烯酸（Epoxyeicosatrienoic acids，ESTs），其洗脱保留时间与合成制备的5，6-、8，9-和11，12-ESTs相同。这些化合物以剂量依赖性方式扩张了猫脑动脉。在线粒体组分中未发现环氧化物形成，并且依赖于NADPH的存在。8，9-EET和11，12-EET的最大效应大于5，6-EET。通过检测8，9-EET和11，12-EET对猫脑动脉新鲜分离的血管肌细胞K+通道活性的影响，进一步研究了这种血管舒张作用的细胞基础。8，9-EET和11，12-EET都增加了在细胞附着模式下记录的98-pS K+通道的开放频率、平均开放时间和开放状态概率，其中在移液管中使用145 mM KCl，在浴中使用4.7 mM KCl。用四乙基铵阻断K+通道活动可减弱11，12-EET对猫脑动脉的舒张作用。这些结果表明，内源性形成的内皮素可能通过激活K+通道的机制，通过扩张脑动脉参与脑血流的局部调节。
Microsomal preparations of cat brain incubated with [C-14]arachidonic acid produced epoxyeicosatrienoic acids (EETs) that eluted with the same retention times as synthetically prepared 5,6-, 8,9-, and 11,12-EETs. These compounds dilated serotonin-preconstricted, pressurized cat cerebral arteries in a dose-dependent fashion. Epoxide formation was not found in mitochondrial fractions and was dependent on the presence of NADPH. The maximum effects of 8,9-EET and 11,12-EET were greater than those of 5,6-EET. The cellular basis of this vasodilation was further investigated by examining the effects of 8,9-EET and 11,12-EET on K+ channel activity in vascular muscle cells freshly isolated from cat cerebral arteries. Both 8,9-EET and 11,12-EET increased the frequency of opening, mean open time, and open-state probability of a 98-pS K+ channel recorded in the cell-attached mode with 145 mM KCl in the pipette and 4.7 mM KCl in the bath. Blockade of K+ channel activity with tetraethylammonium attenuated the vasodilatory effects of 11,12-EET on serotonin-preconstricted cat cerebral arteries. These results suggest that endogenously formed EETs may participate in local regulation of cerebral blood flow by dilating cerebral arteries through a mechanism that involves activation of K+ channels.