Differential effects of 5,6-EET on segmental pulmonary vasoactivity in the rabbit
Differential effects of 5,6-EET on segmental pulmonary vasoactivity in the rabbit
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DOI：
10.1152/ajpheart.00844.2002
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发表时间：
2003-06-01
影响因子：
4.8
通讯作者：
Lonigro, AJ
中科院分区：
文献类型：
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作者：
Stephenson, AH;Sprague, RS;Lonigro, AJ
在兔中，5，6-环氧二十碳三烯酸（EET）据报道既扩张又收缩肺血管。我们认为，这些看似矛盾的结果可以解释为大电导肺动脉（PA）与较小的PA和阻力血管相比，对5，6-EET的反应差异。因此，我们发现，在叶外PA环[>2 mm外径（OD）]中，其中主动张力已被PGF（2 α）增加，5，6-EET以浓度和环氧合酶（考克斯）依赖性方式产生舒张。相反，5，6-EET增加了叶内（1- 2-mm OD）PA的张力。小的叶外PA（2- 2.5-mm OD）表现出中等反应。在完整肺中，5，6-EET（1 x 10（-8）-1 x 10（-5）M）的净效应是肺血管阻力（PVR）从13.0 +/- 0.5增加至47.8 +/- 4.6 mmHg. 100 ml（-1）.min（-1）（EC 50 5.9 +/- 1.7 x 10（-7）M）。PVR的增加伴随着灌注液血栓素（TX）B-2浓度的10倍增加。吲哚美辛（100 μ M）（一种环氧合酶抑制剂）或ONO-3708（20 μ M）（一种TX/PGH（2）（TP）受体拮抗剂）可阻止5，6-EET诱导的PVR增加，但OKY-046（700 μ M）（一种TX合成酶抑制剂）不能阻止。这些结果表明，虽然5，6-EET以COX依赖性方式扩张大的叶外PA段，但在完整的兔肺中，5，6-EET产生收缩，这需要合成除TX之外的TP受体的COX依赖性激动剂。
In the rabbit, 5,6-epoxyeicosatrienoic acid (EET) was reported both to dilate and to constrict pulmonary blood vessels. We propose that these seemingly contradictory results could be explained by differences in responses to 5,6-EET in large-conductance pulmonary arteries (PA) compared with smaller PA and resistance vessels. Thus we found that in rings of extralobar PA [>2-mm outside diameter (OD)], in which active tension had been increased with PGF(2alpha), 5,6-EET produced relaxation in a concentration- and cyclooxygenase (COX)-dependent manner. In contrast, 5,6-EET increased tension in intralobar (1- to 2-mm OD) PA. Small extralobar PA (2- to 2.5-mm OD) exhibited intermediate responses. In the intact lung, the net effect of 5,6-EET (1 x 10(-8)-1 x 10(-5) M) was an increase in pulmonary vascular resistance (PVR) from 13.0 +/- 0.5 to 47.8 +/- 4.6 mmHg.100 ml(-1).min(-1) (EC50 5.9 +/- 1.7 x 10(-7) M). The increase in PVR was accompanied by a 10-fold increase in perfusate thromboxane (TX) B-2 concentration. The 5,6-EET-induced increase in PVR was prevented with indomethacin (100 muM), a cyclooxygenase inhibitor, or ONO-3708 (20 muM), a TX/PGH(2) (TP) receptor antagonist, but not with OKY-046 (700 muM), a TX synthase inhibitor. These results demonstrate that although 5,6-EET dilates large extralobar PA segments in a COX-dependent manner, in the intact rabbit lung 5,6-EET produces constriction that requires synthesis of a COX-dependent agonist of the TP receptor other than TX.