雄激素对人脐动脉平滑肌的长期和短期影响

IF 2.9 4区医学 Q2 Medicine

Clinical and Experimental Pharmacology and Physiology Pub Date : 2012-12-22 DOI:10.1111/1440-1681.12047

Paulo A Saldanha, Elisa Cairrão, Cláudio J Maia, Ignacio Verde

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引用次数: 23

摘要

本研究的目的是确定雄激素在调节人脐动脉(HUA)收缩力中的作用。研究了睾酮对HUA张力的短期影响，以及双氢睾酮(DHT)对参与收缩过程的一些蛋白质表达的长期影响。用DHT (2 μmol/L)或对照(乙醇)处理24 h，分析雄激素的基因组效应。DHT处理24 h后，大电导Ca2+激活(BKCa)通道β1亚基mRNA表达升高，l型钙通道α-亚基mRNA表达降低。在器官浴研究中，睾酮(1-100 μmol/L)对DHT和经5-羟色胺、组胺和KCl预处理的HUA环产生类似的松弛反应。然而，睾酮(100 μmol/L)和硝苯地平(10 μmol/L)联合应用在DHT-中获得的松弛反应明显大于药物处理的HUA。结果表明，睾酮的快速血管松弛作用依赖于对照动脉中的BKCa和电压敏感钾(KV)通道活性，而dht处理的HUA仅依赖于KV通道活性。因此，本研究揭示了雄激素对人体动脉的短期和长期影响的研究的重要性。

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Long- and short-term effects of androgens in human umbilical artery smooth muscle

The aim of the present study was to determine the effects of androgens in the regulation of human umbilical artery (HUA) contractility. The short-term effects of testosterone on the tone of the HUA were investigated, as were the long-term effects of dihydrotestosterone (DHT) on the expression of some proteins involved in the contractile process.
Endothelium-denuded HUA were treated for 24 h with DHT (2 μmol/L) or the vehicle control (ethanol) to analyse the genomic effects of androgens.
Twenty-four hour treatment of HUA with DHT increased the mRNA expression of the β₁-subunit of the large-conductance Ca²⁺-activated (BK_Ca) channel and decreased expression of the α-subunit of L-type calcium channels.
In organ bath studies, testosterone (1–100 μmol/L) produced similar relaxant responses in DHT- and vehicle-treated HUA rings precontracted with 5-HT, histamine and KCl. However, the relaxation response obtained by the combined application of testosterone (100 μmol/L) and nifedipine (10 μmol/L) was significantly greater in DHT- compared with vehicle-treated HUA.
The results indicate that the rapid vasorelaxant effects of testosterone that are dependent on both BK_Ca and voltage-sensitive potassium (K_V) channel activity in control arteries become dependent solely on K_V channel activity in DHT-treated HUA. Thus, the present study reveals the importance of the investigation of both the short- and long-term effects of androgens in human arteries.

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来源期刊

Clinical and Experimental Pharmacology and Physiology 医学-生理学

CiteScore

6.20

自引率

0.00%

发文量

128

审稿时长

6 months

期刊介绍： Clinical and Experimental Pharmacology and Physiology is an international journal founded in 1974 by Mike Rand, Austin Doyle, John Coghlan and Paul Korner. Our focus is new frontiers in physiology and pharmacology, emphasizing the translation of basic research to clinical practice. We publish original articles, invited reviews and our exciting, cutting-edge Frontiers-in-Research series’.