17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage
17β-Estradiol modulates vasoconstriction induced by endothelin-1 following trauma-hemorrhage
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DOI：
10.1152/ajpheart.00809.2006
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发表时间：
2007-01-01
影响因子：
4.8
通讯作者：
Chaudry, Irshad H.
中科院分区：
文献类型：
--
作者：
Ba, Zheng F.;Lu, Ailing;Chaudry, Irshad H.
虽然内皮素-1（ET- 1）诱导血管收缩，但创伤-出血后17 β-雌二醇（E-2）治疗是否改变了ET- 1诱导的血管收缩作用仍不清楚。此外，特定雌激素受体（ER）亚型（ER-α和ER-β）的作用和E-2作用的内皮定位下游机制仍不清楚。我们假设，E-2通过ER-β介导的途径减弱创伤-出血后ET-1诱导的血管收缩。为了研究这一点，在创伤-出血后用或不用E-2处理的雄性Sprague-Dawley大鼠中分离主动脉环，并在体外测定张力的变化。测定对ET- 1的剂量-反应曲线，并测定E-2、丙基吡唑三醇（PPT，ER-α激动剂）和二芳基丙腈（DPN，ER-β激动剂）的血管活性。结果显示，创伤-出血显著增加ET- 1诱导的血管收缩;然而，给予E-2使创伤-出血血管中ET- 1诱导的血管收缩恢复至假手术对照水平。ER-α激动剂DPN抵消ET- 1诱导的血管收缩，而ER-α激动剂PPT无效。此外，在内皮剥脱的主动脉环或用一氧化氮（NO）合酶抑制剂预处理的环中未观察到E-2的血管舒张作用。吲哚美辛抑制环氧合酶对E-2的作用没有影响。因此，E-2给药通过依赖于内皮衍生的NO合成的ER-β介导的途径减弱创伤-出血后ET- 1诱导的血管收缩。
Although endothelin- 1 ( ET- 1) induces vasoconstriction, it remains unknown whether 17 beta- estradiol ( E-2) treatment following trauma- hemorrhage alters these ET- 1-induced vasoconstrictive effects. In addition, the role of the specific estrogen receptor ( ER) subtypes ( ER-alpha and ER-beta) and the endothelium-localized downstream mechanisms of actions of E-2 remain unclear. We hypothesized that E-2 attenuates increased ET-1-induced vasoconstriction following trauma- hemorrhage via an ER-beta-mediated pathway. To study this, aortic rings were isolated from male Sprague-Dawley rats following trauma- hemorrhage with or without E-2 treatment, and alterations in tension were determined in vitro. Dose-response curves to ET- 1 were determined, and the vasoactive properties of E-2, propylpyrazole triol ( PPT, ER-alpha agonist), and diarylpropionitrile ( DPN, ER-beta agonist) were determined. The results showed that trauma- hemorrhage significantly increased ET- 1- induced vasoconstriction; however, administration of E-2 normalized ET- 1-induced vasoconstriction in trauma- hemorrhage vessels to the sham-operated control level. The ER-alpha agonist DPN counteracted ET- 1-induced vasoconstriction, whereas the ER-alpha agonist PPT was ineffective. Moreover, the vasorelaxing effects of E-2 were not observed in endothelium-denuded aortic rings or by pretreatment of the rings with a nitric oxide ( NO) synthase inhibitor. Cyclooxygenase inhibition with indomethacin had no effect on the action of E-2. Thus, E-2 administration attenuates ET- 1- induced vasoconstriction following trauma- hemorrhage via an ER-beta- mediated pathway that is dependent on endothelium- derived NO synthesis.