Comparable vasorelaxant effects of 17 alpha- and 17 beta-oestradiol on ratmesenteric resistance arteries: an action independent of the oestrogen receptor

17 beta-Oestradiol (17 beta E-2) has vasorelaxant properties that may contr ibute to its beneficial cardiovascular effects. The mechanism of vasorelaxa tion remains controversial, but does not appear to involve interaction of 1 7 beta E-2 with its nuclear receptor. The present study examined the effect s on resistance arteries of 17 beta E-2 and its isomer, 17 alpha-oestradiol (17 alpha E-2), which does not bind to the classical oestrogen receptor. I n arteries precontracted with either noradrenaline or KCl, 17 beta E-2 and 17 alpha E-2 caused comparable relaxation in a concentration-dependent mann er over the concentration range 0.1-10 mu mol/l, with no significant differ ence in the maximal effect obtained. Pre-incubation of the arteries with 17 beta E-2 or 17 alpha E-2 for 15 min reduced the magnitude and duration of the force generated with both noradrenaline and KCl to a comparable degree. Vasorelaxation induced by either 17 beta E-2 or 17 alpha E-2 was not block ed by an inhibitor of NO synthase or by protein synthesis inhibitors, indic ating that vasodilatation is not dependent upon either NO generation or pro tein synthesis. In the absence of extracellular calcium, both oestradiols s till relaxed arteries precontracted with NA, suggesting that they inhibit i ntracellular calcium release. Both 17 beta E-2 and 17 alpha E-2 therefore h ave important and comparable vasorelaxant properties that do not require in teraction with the nuclear oestrogen receptor. Direct interactions with the cell membrane or with ion-channel proteins may be responsible.