20-HYDROXYEICOSATETRAENOIC ACID IS AN ENDOGENOUS VASOCONSTRICTOR OF CANINE RENAL ARCUATE ARTERIES
20-HYDROXYEICOSATETRAENOIC ACID IS AN ENDOGENOUS VASOCONSTRICTOR OF CANINE RENAL ARCUATE ARTERIES
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DOI：
10.1161/01.res.72.1.126
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发表时间：
1993-01-01
影响因子：
20.1
通讯作者：
ROMAN, RJ
中科院分区：
文献类型：
--
作者：
MA, YH;GEBREMEDHIN, D;ROMAN, RJ
最近的研究表明，肾动脉可以产生20-羟基二十碳四烯酸（20-HETE），并建议花生四烯酸的P450代谢产物在犬肾动脉的肌源性激活的潜在参与。本文研究了20-HETE对离体犬肾弓状动脉的作用。将浓度为0.01-1 μ M的20-HETE施用于浴槽或管腔，会导致这些血管的直径逐渐减小。相反，19（R）-HETE是血管扩张剂，而19（S）-HETE相对无活性。环氧合酶抑制剂吲哚美辛、内过氧化物/血栓素受体拮抗剂SQ 29548或联合使用吲哚美辛、黄芩素和7-乙氧基试卤灵阻断环氧合酶、脂氧合酶和P450通路均未改变对20-HETE的血管收缩反应。对20-HETE的反应与肾血管平滑肌细胞的去极化和细胞内钙浓度的持续增加有关。膜片钳研究表明，20-HETE显着减少平均开放时间，开放状态的概率，和开放的频率记录从肾血管平滑肌细胞在细胞贴附模式的117 pS的K+通道。用[C-14]花生四烯酸孵育时，从犬肾皮质制备的微粒体产生20-HETE和20-羧基花生四烯酸。这些结果表明，20-HETE是一种内源性收缩犬肾弓状动脉。对20-HETE的血管收缩反应类似于透壁压升高后这些血管的肌源性激活，并表明这种物质在调节肾血管张力中的潜在作用。
Recent studies have indicated that renal arteries can produce 20-hydroxyeicosatetraenoic acid (20-HETE) and suggest the potential involvement of a P450 metabolite of arachidonic acid in the myogenic activation of canine renal arteries. In the present study, the effects of 20-HETE on isolated canine renal arcuate arteries were studied. Administration of 20-HETE to the bath or the lumen at concentrations of 0.01-1 muM produced a graded reduction in the diameter of these vessels. In contrast, 19(R)-HETE was a vasodilator, whereas 19(S)-HETE was relatively inactive. The vasoconstrictor response to 20-HETE was not altered by the cyclooxygenase inhibitor indomethacin, endoperoxide/thromboxane receptor antagonist SQ29548, or combined blockade of the cyclooxygenase, lipoxygenase, and P450 pathways using indometh-acin, baicalein, and 7-ethoxyresorufin. The response to 20-HETE was associated with depolarization and a sustained increase in the intracellular calcium concentration in renal vascular smooth muscle cells. Patch-clamp studies indicated that 20-HETE significantly reduced mean open time, the open-state probability, and the frequency of opening of a 117-pS K+ channel recorded from renal vascular smooth muscle cells in the cell-attached mode. Microsomes prepared from the renal cortex of dogs produced 20-HETE and 20-carboxyarachidonic acid when incubated with [C-14]arachidonic acid. These results indicate that 20-HETE is an endogenous constrictor of canine renal arcuate arteries. The vasoconstrictor response to 20-HETE resembles the myogenic activation of these vessels after elevations in transmural pressure and suggests a potential role for this substance in the regulation of renal vascular tone.