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

ABSTRACT

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 ß(1)-subunit of the large-conductance Ca(2+)-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.