期刊
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
卷 40, 期 3, 页码 181-189出版社
WILEY
DOI: 10.1111/1440-1681.12047
关键词
androgens; calcium channels; potassium channels; smooth muscle cell; vasorelaxation
资金
- Fundacao para a Ciencia e a Tecnologia (Portugal) through the COMPETE program [PEst-C/SAU/UI0709/2011]
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 24h with DHT (2mol/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 1-subunit of the large-conductance Ca2+-activated (BKCa) channel and decreased expression of the -subunit of L-type calcium channels. In organ bath studies, testosterone (1100mol/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 (100mol/L) and nifedipine (10mol/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 BKCa and voltage-sensitive potassium (KV) channel activity in control arteries become dependent solely on KV 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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