title: Comparable vasorelaxant effects of 17alpha- and 17beta-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.
authors.affiliation: Diabetes and Endocrinology Research Unit, Department of Medicine, University of Liverpool, Daulby Street, Liverpool L69 3GA, U.K. Naderali@liverpool.ac.uk
authors.forename: E K
authors.initials: EK
authors.lastname: Naderali
authors.forename: A B
authors.initials: AB
authors.lastname: Walker
authors.forename: P
authors.initials: P
authors.lastname: Doyle
authors.forename: G
authors.initials: G
authors.lastname: Williams
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D020033:Protein Isoforms; D011500:Protein Synthesis Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D003609:Dactinomycin; D011691:Puromycin; D004958:Estradiol; D011189:Potassium Chloride; D003513:Cycloheximide; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine