title: Functional characterization and sex differences in small mesenteric arteries of the estrogen receptor-beta knockout mouse.
abstract: The role of the estrogen receptor (ER) subtypes in the modulation of vascular function is poorly understood. The aim of this study was to characterize ex vivo the functional properties of small arteries and their response to estrogens in the mesenteric circulation of female and male ER-beta knockout mice (beta-ERKO) and their wild-type (WT) littermates. Responses to changes in intraluminal flow and pressure were obtained before and after incubation with 17beta-estradiol or ER-alpha agonist propyl-pyrazole-triol (3 h; 10 nM). Cumulative concentration-response curves to acetylcholine, norepinephrine, and passive distensibility were compared with respect to sex and genotype. The collagen and elastin content within the vascular wall and ER expression were also determined. Endothelial morphology was visualized by scanning electron microscopy. 17beta-Estradiol and propyl-pyrazole-triol-treated arteries from female beta-ERKO and WT mice showed enhanced flow-mediated dilation, but this was not evident in males. Distensibility was decreased in arteries from beta-ERKO females. Sex differences in myogenic tone were observed in 17beta-estradiol-treated arteries, but were similar between beta-ERKO and WT mice. Acetylcholine- and norepinephrine-induced responses were similar between groups and sexes. ER-alpha was similarly expressed in the endothelium and media of arteries from all groups studied, as well as ER-beta in WT animals. Endothelial morphology was similar in arteries from animals of both sexes and genotype; however, arterial elastin content was decreased, and collagen content was increased in beta-ERKO male compared with WT male and with beta-ERKO female. We suggest that ERs play a sex-specific role in estrogen-mediated flow responses and distensibility, and that deletion of ER-beta affects artery structure but only in male animals. Further studies in beta-ERKO mice with established hypertension and in alpha-ERKO mice are warranted.
authors.affiliation: Maternal and Fetal Research Unit, Division of Reproduction and Endocrinology, Kings College London, London, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Douglas
authors.forename: M Natalia
authors.initials: MN
authors.lastname: Cruz
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.forename: Jan-Ake
authors.initials: JA
authors.lastname: Gustafsson
authors.forename: Karolina
authors.initials: K
authors.lastname: Kublickiene
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D003094:Collagen / Q000378:metabolism; D004549:Elastin / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009638:Norepinephrine / Q000494:pharmacology; D012039:Regional Blood Flow / Q000502:physiology; D012727:Sex Characteristics; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D003094:Collagen; D004549:Elastin; D000109:Acetylcholine; D009638:Norepinephrine