title: The oestrogen receptor beta contributes to sex related differences in endothelial function of murine small arteries via EDHF.
abstract: Sex related differences in cardiovascular function have been reported in oestrogen receptor beta knockout (ERbetaKO) mice. In this study we examined the role of endothelium-derived hyperpolarizing factor (EDHF) in differences in small artery endothelial function between ERbetaKO and wild-type (WT) mice. Small femoral arteries were isolated from ERbetaKO and WT mice and mounted on a wire myograph. Concentration-response curves to ACh were compared before and after incubation with inhibitors of nitric oxide (NO) and prostacyclin (PGI2) synthesis. Comparison of the expression of the principal vascular connexins (Cx37, 40 and 43), implicated in EDHF-mediated dilatation were undertaken by immunohistochemistry. Vascular ultrastructure was studied by transmission and scanning electron microscopy. ACh-induced relaxation of arteries (< 200 microm internal diameter) was greater in WT females versus males and was attributable to a greater EDHF component of relaxation. This sex difference was absent in ERbetaKO mice. Arteries from ERbetaKO males (but not females) were more sensitive to ACh compared to WT. The pharmacological evidence and morphological prerequisite for involvement of gap junctions in EDHF-mediated responses was confirmed in male arteries. The absence of ERbeta had no influence on expression of main Cx subtypes within vascular wall or on ultrastructure and morphology of the endothelium. The data suggest that in WT male mice, ERbeta reduces EDHF-mediated relaxation through gap junction communication.
authors.affiliation: Institution for Clinical Science, Intervention and Technology (CLINTEC), Department of Obstetrics and Gynecology, Karolinska Institute, Karolinska University Hospital-Huddinge campus, 14186 Stockholm, Sweden.
authors.forename: Leonid
authors.initials: L
authors.lastname: Luksha
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.forename: Karolina
authors.initials: K
authors.lastname: Kublickiene
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D001685:Biological Factors / Q000502:physiology*; D049628:Body Size; D017630:Connexins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D047629:Estrogen Receptor beta / Q000172:deficiency / Q000502:physiology*; D005260:Female; D005263:Femoral Artery / Q000187:drug effects / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D017629:Gap Junctions / Q000502:physiology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D009569:Nitric Oxide / Q000502:physiology; D012727:Sex Characteristics; D012737:Sex Factors; D013194:Staining and Labeling; D014018:Tissue Distribution; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D017630:Connexins; D047629:Estrogen Receptor beta; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D016718:Arachidonic Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; D000109:Acetylcholine