Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries.
Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries.
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DOI：
10.1152/ajplung.2000.278.2.l335
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发表时间：
2000-02
期刊：
影响因子：
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通讯作者：
Daling Zhu;M. Bousamra;D. Zeldin;J. Falck;M. Townsley;D. Harder;R. Roman;Elizabeth R. Jacobs
中科院分区：
文献类型：
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作者：
Daling Zhu;M. Bousamra;D. Zeldin;J. Falck;M. Townsley;D. Harder;R. Roman;Elizabeth R. Jacobs
关于肺中环氧二十碳三烯酸（E3）的血管活性作用的信息很少。我们证明，5，6-，8，9-，11，12-和14，15-雌二醇以浓度依赖性方式收缩加压兔肺动脉。吲哚美辛或布洛芬（10（-5）M）、SQ-29548、内皮剥脱或血栓素模拟物U-46619的次最大预收缩可阻断5，6-EET甲酯或14，15-EET的收缩。用环氧合酶抑制剂N-甲磺酰基-6-（2-炔丙氧基苯基）己酰胺治疗可减弱肺动脉环对苯乙酮的收缩。肺动脉和外周肺微粒体将花生四烯酸代谢为产物，这些产物在反相HPLC上与5，6-、8，9-、11，12-和14，15-雌二醇的真实区域异构体共迁移，但未证实雌二醇的环氧合酶产物。CYP 2B、CYP 2 E、CYP 2 J、CYP 1A和CYP 2C亚家族蛋白存在于肺动脉和外周肺微粒体中。离体兔肺动脉对雌二醇的收缩是非区域选择性的，依赖于完整的内皮和环氧合酶，与升压前列腺素类化合物的形成一致。这些数据提高了Ehrs可能有助于调节肺血管张力的可能性。
Little information is available regarding the vasoactive effects of epoxyeicosatrienoic acids (EETs) in the lung. We demonstrate that 5, 6-, 8,9-, 11,12-, and 14,15-EETs contract pressurized rabbit pulmonary arteries in a concentration-dependent manner. Constriction to 5,6-EET methyl ester or 14,15-EET is blocked by indomethacin or ibuprofen (10(-5) M), SQ-29548, endothelial denuding, or submaximal preconstriction with the thromboxane mimetic U-46619. Constriction of pulmonary artery rings to phenylephrine is blunted by treatment with the epoxygenase inhibitor N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide. Pulmonary arteries and peripheral lung microsomes metabolize arachidonate to products that comigrate on reverse-phrase HPLC with authentic regioisomers of 5,6-, 8,9-, 11,12-, and 14,15-EETs, but no cyclooxygenase products of EETs could be demonstrated. Proteins of the CYP2B, CYP2E, CYP2J, CYP1A, and CYP2C subfamilies are present in pulmonary artery and peripheral lung microsomes. Constriction of isolated rabbit pulmonary arteries to EETs is nonregioselective and depends on intact endothelium and cyclooxygenase, consistent with the formation of a pressor prostanoid compound. These data raise the possibility that EETs may contribute to regulation of pulmonary vascular tone.