Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue
Human pulmonary arteries dilate to 20-HETE, an endogenous eicosanoid of lung tissue
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DOI：
10.1152/ajplung.1997.272.5.l823
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发表时间：
1997-05-01
影响因子：
4.9
通讯作者：
Jacobs, ER
中科院分区：
文献类型：
--
作者：
Birks, EK;Bousamra, M;Jacobs, ER
我们研究了细胞色素P-450（cP 450）4A途径的花生四烯酸代谢产物20-羟基二十碳四烯酸（SO-HETE）对人肺动脉张力的影响。80-HETE引起的剂量依赖性和吲哚美辛非依赖性的血管舒张离体肺小动脉。全肺微粒体将[C-14]花生四烯酸代谢为SO-HETE和各种白三烯、环氧二十碳三烯酸和前列腺素类。吲哚美辛阻断前列腺素类的形成，而不影响花生四烯酸转化为20-HETE。80-HETE被肺微粒体转化为前列腺素类，提高了20-HETE可能被血管组织中的环氧合酶代谢为血管舒张化合物的可能性。用cP 450 4A的多克隆抗体探测的蛋白质印迹鉴定了在大鼠肝脏中与cP 450 4A免疫学相似的50 kDa的蛋白质。我们的结论是，从人肺的小动脉扩张后暴露于80-HETE在环加氧酶依赖的方式和合成该产品所需的蛋白质和酶活性存在于肺。我们的观察结果表明，cP 450酶产物可能是肺血管张力的内源性调节剂。
We investigated the effect of 20-hydroxyeicosatetraenoic acid (SO-HETE), an arachidonic acid metabolite of the cytochrome P-450 (cP450) 4A pathway, on human pulmonary arterial tone. 80-HETE elicited a dose-dependent and indomethacin-inhibitable vasodilation of isolated small pulmonary arteries. Whole lung microsomes metabolized [C-14]arachidonic acid into SO-HETE and a variety of leukotrienes, epoxyeicosatrienoic acids, and prostanoids. Indomethacin blocked formation of prostanoids without effects on the conversion of arachidonate into 20-HETE. 80-HETE was converted by lung microsomes into prostanoids, raising the possibility that 20-HETE may be metabolized by cyclooxygenase enzymes in vascular tissue to a vasodilatory compound. Western blots probed with a polyclonal antibody to cP450 4A identified a protein of similar to 50 kDa immunologically similar to the cP450 4A in rat liver. We conclude that small arteries from human lungs dilate upon exposure to 80-HETE in a cyclooxygenase-dependent manner and that the proteins and enzymatic activity required to synthesize this product are present in lungs. Our observations suggest that cP450 enzyme products could be endogenous modulators of pulmonary vascular tone.