title: Sex-difference in expression and function of beta-adrenoceptors in macrovessels: role of the endothelium.
abstract: Estrogen modulates adrenergic reactivity of macrovessels, resulting in weaker α-adrenergic vasoconstriction in females than males. However, the mechanisms governing this important sex-specific difference are not well understood. We hypothesized that vessels of females express more dilatory β-adrenoceptors, which counteract constrictive effects of α-adrenoceptors. This hypothesis was tested using aortas of normotensive (WKY) and hypertensive rats (SHR), along with human mammary artery. Selective blockade of β1(CGP20712) or β3(SR59230A), but not β2(ICI118,551) adrenoceptors, greatly increased α-adrenergic constriction (norepinephrine) of aorta in female SHRs, but not in male SHRs at 12 weeks of age. Consistently, the selective β1/β2(isoproterenol) and β3-adrenergic (BRL37344) relaxation was stronger in female SHRs than in males. Removal of endothelium and use of L-NMMA abolished sex-difference in α-adrenergic constriction and β-adrenergic relaxation. Immunostainings revealed endothelial localization of β1- and β3-adrenoceptors. mRNA levels of aortic β1- and β3-, but not β2-adrenoceptors were markedly higher in female than in male SHRs. The sex-specific differences in α-adrenergic constriction and β-adrenoceptor mRNA levels were age-dependent, predominantly present up to 29 weeks and disappeared at 36 weeks of age. The sex-specific difference was not strain-dependent and was similarly present in normotensive WKY rats. Human mammary artery of women showed a weaker α-adrenergic constriction than arteries of men. This sex-specific difference was prominent at 45-65 years and disappeared with aging. Our results convincingly demonstrate that female macrovessels express more dilatory β1- and β3-adrenoreceptors than male vessels with a predominant endothelial localization. This sex-specific difference is functionally relevant in young adults and is attenuated with aging.
authors.affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Suzan
authors.initials: S
authors.lastname: Al-Gburi
authors.affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany. Andreas.Deussen@tu-dresden.de.
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
authors.affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Zatschler
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Silvio
authors.initials: S
authors.lastname: Weber
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Künzel
authors.affiliation: Department of Pharmacology and Toxicology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: Ali
authors.initials: A
authors.lastname: El-Armouche
authors.affiliation: Leibniz-Institut fuer Analytische Wissenschaften, ISAS, e.V, Dortmund, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Lorenz
authors.affiliation: Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Cybularz
authors.affiliation: Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, Dresden, Germany.
authors.forename: Henning
authors.initials: H
authors.lastname: Morawietz
authors.affiliation: Department of Physiology, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany.
authors.forename: Irakli
authors.initials: I
authors.lastname: Kopaliani
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000368:Aged; D000375:Aging / Q000378:metabolism*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D051381:Rats; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta
keywords: Beta-adrenoceptors; Human mammary artery; Sex-difference; Vascular endothelium; Vascular tone regulation