title: Long-term treatment with Nandrolone Decanoate impairs mesenteric vascular relaxation in both sedentary and exercised female rats.
abstract: Nandrolone Decanoate (ND) is an Anabolic Androgenic Steroid (AAS) that under abusive regimen can lead to multiple physiological adverse effects. Studies of AAS-mediated cardiovascular (CV) alterations were mostly taken from male subjects, even though women are also susceptible to the effects of AAS and gender-specific differences in susceptibility to vascular diseases exist. Here we investigate ND-induced vascular reactivity alterations in both sedentary and exercised female rats and whether these alterations depend on endothelium-derived factors. We show that chronic exposure of female Wistar rats to ND (20mg/Kg/week for 4weeks) impaired the vascular mesenteric bed (MVB) reactivity to vasodilator (acetylcholine) agonist. The endothelium-dependent Nitric Oxide (NO) component was reduced in ND-treated rats, whereas neither the endothelium-derived hyperpolarizing factor (EDHF) component nor prostanoids were altered in the MVBs. Endothelial dysfunction observed in ND-treated rats was associated with decreased eNOS (Ser1177) and Akt (Ser473) phosphorylation sites and upregulation of iNOS and NADPH oxidase expression. Exercise training by weight lifting in water did not improve the vascular alterations induced by ND treatment. ND treatment also significantly reduced the serum levels of estradiol in females, overriding its CV protective effect. These results help uncover the role of ND modulating endothelial function in the setting of CV disease caused by the abuse of AAS in females. If this translates to humans, young women abusing AAS can potentially lose the cardio protective effect rendered by estrogen and be more susceptible to CV alterations.
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil. Electronic address: icaliman12@gmail.com.
authors.forename: Izabela F
authors.initials: IF
authors.lastname: Caliman
authors.affiliation: Department of Anatomy & Cell Biology, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA; Program in Medical Neurosciences, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Cristian S
authors.initials: CS
authors.lastname: Bernabe
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Antônio F
authors.initials: AF
authors.lastname: de Melo
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Girlândia A
authors.initials: GA
authors.lastname: Brasil
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Andrews M
authors.initials: AM
authors.lastname: do Nascimento
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil; Department of Pharmaceutical Sciences, University of Vila Velha, Vila Velha, ES, Brazil.
authors.forename: Ewelyne M
authors.initials: EM
authors.lastname: de Lima
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Suely G
authors.initials: SG
authors.lastname: Figueiredo
authors.affiliation: Department of Pharmaceutical Sciences, University of Vila Velha, Vila Velha, ES, Brazil.
authors.forename: Tadeu U
authors.initials: TU
authors.lastname: de Andrade
authors.affiliation: Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo, Brazil.
authors.forename: Nazaré S
authors.initials: NS
authors.lastname: Bissoli
mesh_terms: D050154:Adiposity / Q000187:drug effects; D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005260:Female; D008638:Mesenteric Arteries / Q000187:drug effects; D008954:Models, Biological; D019255:NADPH Oxidases / Q000378:metabolism; D009277:Nandrolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077603:Nandrolone Decanoate; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
chemical_list: D045930:Anabolic Agents; D001685:Biological Factors; D011453:Prostaglandins; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D009277:Nandrolone; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases; D000077603:Nandrolone Decanoate
keywords: Anabolic Androgenic Steroids; Exercise training; Nandrolone Decanoate; Nitric Oxide; Vascular dysfunction