20-HETE agonists and antagonists in the renal circulation
20-HETE agonists and antagonists in the renal circulation
复制标题
DOI：
10.1152/ajprenal.1999.277.5.f790
复制
发表时间：
1999-11-01
影响因子：
4.2
通讯作者：
Roman, RJ
中科院分区：
文献类型：
--
作者：
Alonso-Galicia, M;Falck, JR;Roman, RJ
本研究检测了一系列20-羟基二十碳四烯酸(20-HETE)衍生物对肾小动脉直径的影响，以确定20-HETE对血管收缩反应的结构要求。本文观察了大鼠肾小叶间动脉(65-125微米)对5-，8-，12-，15-，19-，20-，21-HETE，花生四烯酸(AA)和饱和、部分饱和的20-HETE(10(-8)~10(-6)M)衍生物的血管反应。20-HETE、21-HETE、二甲基-20-HETE和20-HETE的部分饱和衍生物20-羟基-5(Z)、14(Z)-二烯酸分别使血管直径减小19+/-3、17+/-3、16+/-2和28+/-2%。相反，5-、8-、12-、15-和19-HETE、AA、饱和、部分饱和、羧基和20-HETE的19-碳衍生物对血管直径没有影响。预先给予5-、15-和19-HETE、Ig-碳衍生物或20-羟基-6(Z)、15(Z)-二烯酸(1 MU M)可完全阻断20-HETE对肾小动脉的收缩反应。用AA、羧基、饱和19碳和饱和20-HETE衍生物(1mU M)部分阻断这一反应，而8-和12-HETE(1mU M)对20-HETE的血管收缩反应无影响。这些发现表明，20-HETE激动剂和拮抗剂需要碳1上的羧基或可电离基团以及14或15碳附近的双键。20-HETE激动剂也需要能够在碳20或21上氢键的官能团，而拮抗剂缺乏这个反应性基团。
The present study examined the effects of a series of 20-hydroxyeicosatetraenoic acid (20-HETE) derivatives on the diameter of renal arterioles to determine the structural requirements of the vasoconstrictor response to 20-HETE. The vascular responses to 5-, 8-, 12-, 15-, 19-, 20-, 21-HETEs, arachidonic acid (AA), and saturated, partially saturated, dimethyl, carboxyl, and 19-carbon derivatives of 20-HETE (10(-8) to 10(-6) M) were assessed in rat renal interlobular arteries (65-125 mu m). 20-HETE, 21-HETE, dimethyl-20-HETE, and a partially saturated derivative of 20-HETE, 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid, reduced vessel diameter by 19 +/- 3, 17 +/- 3, 16 +/- 2, and 28 +/- 2%, respectively. In contrast, 5-, 8-, 12-, 15-, and 19-HETE, AA, saturated, partially saturated, carboxyl, and the 19-carbon derivatives of 20-HETE had no effect on vessel diameter. Pretreatment with 5-, 15-, and 19-HETE, the Ig-carbon derivative or 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (1 mu M) completely blocked the vasoconstrictor response to 20-HETE in renal arterioles. Pretreatment with AA, carboxyl, saturated 19-carbon, and saturated 20-HETE derivatives (1 mu M) partially blocked the response, whereas 8- and 12-HETE (1 mu M) had no effect on the vasoconstrictor response to 20-HETE. These findings suggest that 20-HETE agonists and antagonists require a carboxyl or an ionizable group on carbon 1 and a double bond near the 14 or 15 carbon. 20-HETE agonists also require a functional group capable of hydrogen bonding on carbon 20 or 21, whereas antagonists lack this reactive group.