title: 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 β(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.
authors.affiliation: Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Paulo A
authors.initials: PA
authors.lastname: Saldanha
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairrão
authors.forename: Cláudio J
authors.initials: CJ
authors.lastname: Maia
authors.forename: Ignacio
authors.initials: I
authors.lastname: Verde
mesh_terms: D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000096:biosynthesis; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000096:biosynthesis; D009119:Muscle Contraction / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D014469:Umbilical Arteries / Q000187:drug effects* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D000728:Androgens; D020746:Calcium Channels, L-Type; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D014662:Vasoconstrictor Agents; D013196:Dihydrotestosterone