Effect of Potassium Channels and Endothelium Derived Hyperpolarizing Factor on Vasorelaxant Effect of 17β-Estradiol in Human Saphenous Vein

The vasorelaxant effect of estrogens on blood vessels is one of the important cardiovascular protective mechanisms of estrogen. The present experiments were designed to study the mechanisms of vasorelaxant effect of 17β-estradiol (E2) in human saphenous veins (HSV). HSV were obtained from patients undergoing coronary artery bypass graft surgery in Tabriz Madani Heart Center. The role of K+ channels and endothelium derived hyperpolarizing factor (EDHF) in the effects of E2 were studied by incubating tissues with K+ channels blockers: glibenclamid (3μM), 4-aminopyridin (1mm), tetraethyl ammonium (TEA, at lower and higher concentration: 1mm and 10mM), BaCl2 (30μM) and combination of charybdotoxin and apamin. In order to assess the role of endothelium in the inhibitory effect of TEA (10mM) on the relaxant effect of E2, responses were elicited in endothelium denuded vein rings. TEA at 1mm, (selective inhibitor of large-conductance, BKCa, Ca2+ activated K+ channels), 4- aminopyridin (selective inhibitor of voltage dependent K+ channels) and glibenclamid (selective inhibitor of ATP dependent K+ channels) did not affect the vasorelaxant effects of E2 on PGF2α-induced contractions. TEA at higher concentration, an inhibitor of small-conductance (SKCa) and intermediate-conductance (IKCa) Ca2+ activated K+ channels, significantly inhibited E2-induced vasorelaxation. This inhibitory effect was endothelium-dependent and abolished by endothelium denuding. In intact tissues, pretreatment either with a combination of charybdotoxin and apamin (inhibitors of EDHF), or BaCl2, significantly reduced the relaxation produced by E2. The data suggest that vasorelaxant effect of E2 in HSV maybe mediated by EDHF which involves apamin/charybdotoxin-sensitive K+-channels and K+.