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

Abstract

17beta-Oestradiol (17betaE(2)) 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 17betaE(2) with its nuclear receptor. The present study examined the effects on resistance arteries of 17betaE(2) and its isomer, 17alpha-oestradiol (17alphaE(2)), which does not bind to the classical oestrogen receptor. In arteries precontracted with either noradrenaline or KCl, 17betaE(2) and 17alphaE(2) caused comparable relaxation in a concentration-dependent manner over the concentration range 0.1-10 micromol/l, with no significant difference in the maximal effect obtained. Pre-incubation of the arteries with 17betaE(2) or 17alphaE(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 17betaE(2) or 17alphaE(2) 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 17betaE(2) and 17alphaE(2) 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.

The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats

“…To exclude possible vascular effects of ethanol, two arteries from each animal in each experiment were studied in the presence of the same volume of ethanol as the test arteries. As reported previously, there was no significant effect of this low concentration of ethanol on contractility induced by either KPSS or NA [29,30].…”

Vasorelaxant effects of oestradiols on guinea pigs: a role for gender differences

“…To exclude possible vascular effects of ethanol, two arteries from each animal in each experiment were studied in the presence of the same volume of ethanol as the test arteries. As previously reported, there was no significant effect of this low concentration of ethanol on contractility induced by either KPSS or NA [9,10,18]…”

“…Several studies have indicated vasorelaxant properties for 17αE 2 [10] and 17βE 2 [8,10,13–15], which are not mediated via interaction with nuclear oestrogen receptors as indicated by their fast onset (a few minutes) and by the ineffectiveness of protein synthesis inhibitors [9,10]. Moreover, the vascular effects of 17αE 2 and 17βE 2 do not involve endothelial NO generation, nor prostacyclin or other vasodilatory prostanoids [9,10,14,21].…”

“…Several studies have indicated vasorelaxant properties for 17αE 2 [10] and 17βE 2 [8,10,13–15], which are not mediated via interaction with nuclear oestrogen receptors as indicated by their fast onset (a few minutes) and by the ineffectiveness of protein synthesis inhibitors [9,10]. Moreover, the vascular effects of 17αE 2 and 17βE 2 do not involve endothelial NO generation, nor prostacyclin or other vasodilatory prostanoids [9,10,14,21]. Rather, 17αE 2 and 17βE 2 may inhibit membrane calcium channels, especially of the l ‐type [9,21–24], and we have recently shown that 17αE 2 and 17βE 2 are equipotent inhibitors of calcium influx in male rat MA [10].…”

“…Recent studies have demonstrated that oestradiols directly induce vasorelaxation and that this may also play a role in cardiovascular protective effects of oestradiols. 17βE 2 has been shown to cause endothelium‐dependent and ‐independent relaxation of isolated arteries from rabbit [6,7], rat [8–10] and pig [11,12], while intra‐arterial infusion of 17βE 2 that achieved physiological circulatory levels potentiated acetylcholine‐induced vasodilatation in both healthy women and in subjects with risk factors for vascular dysfunction [13]. However, in vivo studies have demonstrated that acute, but not chronic, 17βE 2 administration improves vasodilatation in both peripheral and coronary arteries [14,15].…”