title: Dehydroepiandrosterone protects against oxidative stress-induced endothelial dysfunction in ovariectomized rats.
abstract: Cardiovascular disease is less frequent in premenopausal women than in age-matched men or postmenopausal women. Moreover, the marked age-related decline in serum dehydroepiandrosterone (DHEA) level has been associated to cardiovascular disease. The aim of this study was to evaluate the effects of DHEA treatment on vascular function in ovariectomized rats. At 8 weeks of age, female Wistar rats were ovariectomized (OVX) or sham (SHAM) operated and 8 weeks after surgery both groups were treated with vehicle or DHEA (10mg kg⁻¹ week⁻¹) for 3 weeks. Aortic rings were used to evaluate the vasoconstrictor response to phenylephrine (PHE) and the relaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP). Tissue reactive oxygen species (ROS) production and SOD, NADPH oxidase and eNOS protein expression were analysed. PHE-induced contraction was increased in aortic rings from OVX compared to SHAM, associated with a reduction in NO bioavailability. Furthermore, the relaxation induced by ACh was reduced in arteries from OVX, while SNP relaxation did not change. The incubation of aortic rings with SOD or apocynin restored the enhanced PHE-contraction and the impaired ACh-relaxation only in OVX. DHEA treatment corrected the increased PHE contraction and the impaired ACh-induced relaxation observed in OVX by an increment in NO bioavailability and decrease in ROS production. Besides, DHEA treatment restores the reduced Cu/Zn-SOD protein expression and eNOS phosphorylation and the increased NADPH oxidase protein expression in the aorta of OVX rats. The present results suggest an important action of DHEA, improving endothelial function in OVX rats by acting as an antioxidant and enhancing the NO bioavailability.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of S˜ao Paulo, SP, Brazil.
authors.forename: João Paulo Gabriel
authors.initials: JP
authors.lastname: Camporez
authors.forename: Eliana Hiromi
authors.initials: EH
authors.lastname: Akamine
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Davel
authors.forename: Celso Rodrigues
authors.initials: CR
authors.lastname: Franci
authors.forename: Luciana Venturini
authors.initials: LV
authors.lastname: Rossoni
authors.forename: Carla Roberta de Oliveira
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology; D002317:Cardiovascular Agents / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D005260:Female; D019255:NADPH Oxidases / Q000096:biosynthesis; D009569:Nitric Oxide / Q000096:biosynthesis; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D009599:Nitroprusside / Q000494:pharmacology; D010052:Ovariectomy; D018384:Oxidative Stress / Q000187:drug effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis
chemical_list: D000098:Acetophenones; D002317:Cardiovascular Agents; D017382:Reactive Oxygen Species; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; C056165:acetovanillone; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D000109:Acetylcholine