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Abstract:
:Increasing evidence suggests a role for the ET (endothelin) system in preeclampsia. Hence, blocking this system with endothelin receptor antagonists (ERAs) could be a therapeutic strategy. Yet, clinical studies are lacking due to possible teratogenic effects of ERAs. In this study, we investigated the placental transfer of ERAs and their effect on ET-1-mediated vasoconstriction. Term placentas were dually perfused with the selective ETAR (ET type A receptor) antagonists sitaxentan and ambrisentan or the nonselective ETAR/ETBR antagonist macitentan and subsequently exposed to ET-1 in the fetal circulation. ET-1 concentration-response curves after incubation with sitaxentan, ambrisentan, macitentan, or the selective ETBR antagonist BQ-788 were also constructed in isolated chorionic plate arteries using wire-myography, and gene expression of the ET-system was quantified in healthy and early onset preeclamptic placentas. At steady state, the mean fetal-to-maternal transfer ratios were 0.32±0.05 for sitaxentan, 0.21±0.02 for ambrisentan, and 0.05±0.01 for macitentan. Except for BQ-788, all ERAs lowered the response to ET-1, both in the perfused cotyledon and isolated chorionic plate arteries. Placental gene expression of ECE-1, ETAR, and ETBR were comparable in healthy and preeclamptic placentas, while ET-1 expression was higher in preeclampsia. Our study is the first to show direct transfer of ERAs across the term human placenta. Furthermore, ETAR exclusively mediates ET-1-induced constriction in the fetoplacental vasculature. Given its limited transfer, macitentan could be considered as potential preeclampsia therapy. Extending knowledge on placental transfer to placentas of preeclamptic pregnancies is required to determine whether ERAs might be applied safely in preeclampsia.
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最新影响因子:7.713 | 期刊ISSN:0194-911X | CiteScore:5.34 |
出版周期:Monthly | 是否OA:YES | 出版年份:1979 |
期刊官方网址:http://hyper.ahajournals.org/
期刊投稿地址:http://hype-submit.aha-journals.org/cgi-bin/main.plex
自引率:9.70% | 研究方向:医学-外周血管病 |
出版地区:UNITED STATES |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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This journal provides a forum for the presentation of scientific investigation of the highest quality in the broad field of blood pressure regulation and the pathophysiological mechanisms underlying hypertensive diseases.
这本杂志提供了一个论坛,介绍了在广泛的血压调节领域中最高质量的科学研究和高血压疾病的病理生理机制。
大类(学科) | 小类(学科) | 学科排名 |
医学 |
PERIPHERAL VASCULAR DISEASE(周围血管疾病) 1区 |
3/65 |
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
271 | 254 | 17 |
引文计数(2018)
文献(2015-2017)
6818次引用
1276篇文献
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Medicine
小类(学科):Internal Medicine
|
#6/121
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研究方向:医药科学 循环系统 血压调节异常 高血压病
审稿时间: 2个月内
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研究方向:高血压
接受率: 比较困难(25%命中)
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接受率: 比较困难(25%命中)
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研究方向:高血压
接受率: 比较困难(25%命中)
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研究方向:高血压 认知功能
接受率: 比较困难(25%命中)
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研究方向:高血压 心脏 心血管
接受率: 中等(50%命中)
影响因子:1.195
ISSN:1386-2073
研究方向:化学-生化研究方法
影响因子:6.035
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研究方向:医学-临床神经学
影响因子:3.743
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研究方向:CLINICAL NEUROLOGY-PHARMACOLOGY & PHARMACY
影响因子:1.821
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研究方向:医学-传染病学
影响因子:1.661
ISSN:1120-009X
研究方向:医学-药学
影响因子:2.296
ISSN:1076-6294
研究方向:医学-传染病学
影响因子:2.984
ISSN:1178-6973
研究方向:-
影响因子:5.439
ISSN:0305-7453
研究方向:医学-传染病学
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