5,6-epoxyeicosatrienoic acid reduces increases in pulmonary vascular resistance in the dog
5,6-epoxyeicosatrienoic acid reduces increases in pulmonary vascular resistance in the dog
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DOI：
10.1152/ajpheart.1998.275.1.h100
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发表时间：
1998-07-01
影响因子：
4.8
通讯作者：
Lonigro, AJ
中科院分区：
文献类型：
--
作者：
Stephenson, AH;Sprague, RS;Lonigro, AJ
我们最近报道了犬肺微粒体将花生四烯酸代谢为所有四种区域异构体环氧二碳三烯酸（EET）。5,6- eet通常以环氧化酶依赖的方式扩张几种非肺血管床的血管。本研究旨在确定5,6- eet是否可以降低完整肺循环中的肺血管阻力（PVR）。在离体犬肺中灌注生理盐溶液，持续输注U-46619 （3.28 +/- 0.99 nmol/min）使PVR升高62.1 +/- 4.5%。向灌注液中注入5,6- eet （10(-5) M）可使u -46619介导的PVR增加减少23.6 +/- 6.1%。U-46619和5,6- eet的这些作用仅限于肺静脉段的阻力变化。相比之下，5-羟色胺（5-HT）治疗的肺部静脉和动脉段阻力增加。然而，在后一种情况下，5,6- eet降低了动脉节段阻力，而不是静脉节段阻力。5,6- eet使肺PGI(2)合成从70.5 +/- 18.4增加到675.9 +/- 125.4 ng/min。在吲哚美辛（10(-4)M）存在的情况下，5,6- eet不会增加PGI2的合成，也不会降低U-46619或5- mt介导的PVR升高。在犬肺内血管中，5,6- eet降低了U-46619收缩静脉的主动张力。5,6- eet降低了5- ht收缩的动脉的主动张力，但没有降低静脉的主动张力，这与灌注肺的结果一致。这些结果表明，5,6- eet在完整肺循环中是一种血管扩张剂。其扩张活性取决于存在的收缩剂、节段抗性和环加氧酶活性。
We recently reported that canine pulmonary microsomes metabolize arachidonic acid to all four regioisomeric epoxyeicosatrienoic acids (EET). 5,6-EET dilates blood vessels in several nonpulmonary vascular beds, often in a cyclooxygenase-dependent manner. The present study was designed to determine whether 5,6-EET can decrease pulmonary vascular resistance (PVR) in the intact pulmonary circulation. In isolated canine lungs perfused with physiological salt solution, a constant infusion of U-46619 (3.28 +/- 0.99 nmol/min) increased PVR 62.1 +/- 4.5%. Administration of 5,6-EET (10(-5) M) into the perfusate reduced the U-46619-mediated increase in PVR by 23.6 +/- 6.1%. These effects of U-46619 and 5,6-EET were limited to changes in resistance solely in the pulmonary venous segment. In contrast, venous as well as arterial segmental resistances were increased in 5-hydroxytryptamine (5-HT)-treated lungs. However, in the latter instance, 5,6-EET reduced arterial but not venous segmental resistance. 5,6-EET increased pulmonary PGI(2) synthesis from 70.5 +/- 18.4 to 675.9 +/- 125.4 ng/min. In the presence of indomethacin (10(-4) M), 5,6-EET did not increase PGI2 synthesis nor did it decrease U-46619- or 5-MT-mediated increases in PVR. In canine intrapulmonary vessels, 5,6-EET decreased active tension in veins contracted with U-46619. 5,6-EET decreased active tension in arteries but not veins contracted with 5-HT, consistent with results in the perfused lungs. These results demonstrate that 5,6-EET is a vasodilator in the intact pulmonary circulation. Its dilator activity depends on the constrictor agent present, the segmental resistance, and cyclooxygenase activity.