title: Potassium channels are involved in testosterone-induced vasorelaxation of human umbilical artery.
abstract: Recent studies have shown that testosterone induces relaxation of different arteries, although the mechanism of this action is still under debate. We investigated the involvement of potassium channels in this mechanism. Using standard organ bath techniques, rings of human umbilical arteries (HUA) without endothelium were contracted by serotonin (5-HT, 1 microM), histamine (10 microM) and potassium chloride (KCl, 30 and 60 mM), and the vasorelaxant effect of testosterone was analysed. Testosterone (100 microM) relaxed human umbilical arteries contracted with 5-HT (30.1 +/- 3.2%), histamine (55.1 +/- 2.6%), KCl 30 mM (52.9 +/- 8.3%) and KCl 60 mM (54.8 +/- 6.3%). Flutamide (10 microM), an inhibitor of classical intracellular testosterone receptor, and glibenclamide, an ATP-sensitive potassium-channels (K(ATP)) inhibitor, did not influence the testosterone relaxant effect. 4-aminopyridine, a voltage-sensitive potassium-channels (Kv) inhibitor, decreased the effect of testosterone on histamine- and 5-HT-contracted arteries. Tetraethylammonium (TEA), which inhibits Kv channels and large-conductance Ca(2+)-activated potassium channels (BK(Ca)), decreased the effect of testosterone on KCl (60 mM)-contracted and 5-HT-contracted HUA. In conclusion, testosterone induces relaxation of HUA, and this effect does not appear to be mediated via a classic intracellular testosterone receptor-dependent mechanism. Our results suggest that this relaxation is partially mediated by activation of BK(Ca) and K(V) channels. The involvement of these two channels in testosterone-relaxant mechanism is dependent on the pathways activated by the contractile agent used.
authors.affiliation: CICS - Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Av. Infante D. Henrique, 6200-506 Covilhã, Portugal.
authors.forename: Elisa
authors.initials: E
authors.lastname: Cairrão
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Alvarez
authors.forename: António José
authors.initials: AJ
authors.lastname: Santos-Silva
authors.forename: Ignacio
authors.initials: I
authors.lastname: Verde
mesh_terms: D006632:Histamine / Q000494:pharmacology; D006801:Humans; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013739:Testosterone / Q000502:physiology*; D014469:Umbilical Arteries / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
chemical_list: D024681:Potassium Channels, Calcium-Activated; D024642:Potassium Channels, Voltage-Gated; D012701:Serotonin; D013739:Testosterone; D011189:Potassium Chloride; D006632:Histamine