Comparable vasorelaxant effects of 17α- and 17β-oestradiol on rat mesenteric resistance arteries: an action independent of the oestrogen receptor

17β-Oestradiol (17βE₂) has vasorelaxant properties that may contribute to its beneficial cardiovascular effects. The mechanism of vasorelaxation remains controversial, but does not appear to involve interaction of 17βE₂ with its nuclear receptor. The present study examined the effects on resistance arteries of 17βE₂ and its isomer, 17α-oestradiol (17αE₂), which does not bind to the classical oestrogen receptor. In arteries precontracted with either noradrenaline or KCl, 17βE₂ and 17αE₂ caused comparable relaxation in a concentration-dependent manner over the concentration range 0.1–10 μmol/l, with no significant difference in the maximal effect obtained. Pre-incubation of the arteries with 17βE₂ or 17αE₂ 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 17βE₂ or 17αE₂ was not blocked by an inhibitor of NO synthase or by protein synthesis inhibitors, indicating that vasodilatation is not dependent upon either NO generation or protein synthesis. In the absence of extracellular calcium, both oestradiols still relaxed arteries precontracted with NA, suggesting that they inhibit intracellular calcium release. Both 17βE₂ and 17αE₂ therefore have important and comparable vasorelaxant properties that do not require interaction with the nuclear oestrogen receptor. Direct interactions with the cell membrane or with ion-channel proteins may be responsible.