title: Vascular estrogen receptors and endothelium-derived nitric oxide production in the mouse aorta. Gender difference and effect of estrogen receptor gene disruption.
abstract: The present study was designed to test the hypothesis that estrogen receptors (ER) in the blood vessel wall play a role in the modulation of the release of endothelium-derived nitric oxide (EDNO). Both basal and stimulated release of EDNO were determined in aortic rings isolated from female and male wild-type and male homozygous estrogen receptor knock-out (ERKO) mice. 125I-17beta-estradiol binding in aortic tissue showed significantly more high affinity cytosolic- nuclear-binding sites in male compared with female wildtype mice. Estrogen receptor transcripts were present in the aorta of male wild-type mice, but they were absent in male ERKO animals. Basal release of EDNO (determined by endothelium-dependent contraction caused by NG-nitro-arginine) was significantly higher in aorta of wild-type male mice compared with wild-type female mice, and significantly lower in the aorta of male ERKO compared with male wild-type mice. Acetylcholine-induced endothelium-dependent relaxation was similar in all groups studied. No difference was observed in the activity of calcium-dependent nitric oxide synthase in homogenates of lungs and brain taken from male wild-type and ERKO mice. These studies show a significant association between the number of estrogen receptors and basal release of EDNO in the aorta of mice, and suggest that decreased vascular estrogen receptor number may represent a novel risk factor for cardiovascular diseases.
authors.affiliation: Department of Cardiovascular Research, Berlex Biosciences, Richmond, California 94804-0099, USA. gabor_rubanyi@berlex.com
authors.forename: G M
authors.initials: GM
authors.lastname: Rubanyi
authors.forename: A D
authors.initials: AD
authors.lastname: Freay
authors.forename: K
authors.initials: K
authors.lastname: Kauser
authors.forename: D
authors.initials: D
authors.lastname: Sukovich
authors.forename: G
authors.initials: G
authors.lastname: Burton
authors.forename: D B
authors.initials: DB
authors.lastname: Lubahn
authors.forename: J F
authors.initials: JF
authors.lastname: Couse
authors.forename: S W
authors.initials: SW
authors.lastname: Curtis
authors.forename: K S
authors.initials: KS
authors.lastname: Korach
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001011:Aorta / Q000502:physiology; D001921:Brain / Q000201:enzymology; D017931:DNA Primers; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D004790:Enzyme Induction; D004958:Estradiol / Q000097:blood; D005091:Exons; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D012727:Sex Characteristics; D013045:Species Specificity; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D011450:Prostaglandin Endoperoxides, Synthetic; D011960:Receptors, Estrogen; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D004958:Estradiol; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D019001:Nitric Oxide Synthase