title: Nandrolone decanoate determines cardiac remodelling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension.
abstract: The aims of this study were to evaluate the effects of nandrolone (ND) on cardiac inflammatory cytokines, ACE activity, troponin I, and the sensitivity of the Bezold-Jarisch reflex (BJR). Male Wistar rats were administered either ND (20 mg/kg; DECA) or vehicle (control animals; CONT) for 4 weeks. BJR was analyzed by measuring the bradycardia and hypotension responses elicited by serotonin administration (2-32 μg/kg). Mean arterial pressure (MAP) was assessed and myocyte hypertrophy was determined by the heart weight/body weight ratio and by morphometric analysis. Matrix collagen deposition was assessed by histological analysis of the picrosirius red-stained samples. Mesenteric vascular reactivity was performed and central venous pressure (CVP) evaluated. Cardiac inflammatory cytokine levels and angiotensin-converting enzyme (ACE) activity were studied as well the biomarker of cardiac lesion, troponin I. DECA group showed enhancement of matrix type I collagen deposition (p < 0.01) and cardiac ACE activity (p < 0.01) compared with the CONT. Interleukin (IL)-10 was reduced (p < 0.01) and pro-inflammatory cytokines (TNF-α and IL-6; p < 0.01) were increased in the DECA group compared with CONT. Cardiac injury was observed in the DECA group shown by the reduction in cardiac troponin I (p < 0.01) compared with the CONT group. Animals in the DECA group also developed myocyte hypertrophy and reduction of BJR sensitivity. The MAP of animals treated with ND reached hypertensive levels (p < 0.01; compared with CONT). No changes in CVP and vascular reactivity were observed in both experimental groups. We conclude that high doses of ND elicit cardiotoxic effects with cardiac remodelling and injury. Cardiac changes reduce the BJR sensitivity. Together, these abnormalities contributed to the development of hypertension in animals in the DECA group.
authors.affiliation: Department of Pharmacy, University of Vila Velha, Espírito Santo, Brazil.
authors.forename: João Vicente Maggioni
authors.initials: JV
authors.lastname: Franquni
authors.forename: Andrews Marques
authors.initials: AM
authors.lastname: do Nascimento
authors.forename: Eweliny Miranda
authors.initials: EM
authors.lastname: de Lima
authors.forename: Girlândia Alexandre
authors.initials: GA
authors.lastname: Brasil
authors.forename: Otávio Arruda
authors.initials: OA
authors.lastname: Heringer
authors.forename: Karla Oliveira Dos Santos
authors.initials: KO
authors.lastname: Cassaro
authors.forename: Thony Vinicius Pita
authors.initials: TV
authors.lastname: da Cunha
authors.forename: Carlos
authors.initials: C
authors.lastname: Musso
authors.forename: Maria Carmen L F
authors.initials: MC
authors.lastname: Silva Santos
authors.forename: Ieda Carneiro
authors.initials: IC
authors.lastname: Kalil
authors.forename: Denise Coutinho
authors.initials: DC
authors.lastname: Endringer
authors.forename: Giovanna Assis Pereirra
authors.initials: GA
authors.lastname: Boëchat
authors.forename: Nazaré Souza
authors.initials: NS
authors.lastname: Bissoli
authors.forename: Tadeu Uggere
authors.initials: TU
authors.lastname: de Andrade
mesh_terms: D045930:Anabolic Agents / Q000009:adverse effects*; D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D001919:Bradycardia / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D015870:Gene Expression / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D009277:Nandrolone / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077603:Nandrolone Decanoate; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012018:Reflex / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D012891:Sleep Apnea Syndromes / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D019210:Troponin I / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D045930:Anabolic Agents; D015850:Interleukin-6; D019210:Troponin I; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D012701:Serotonin; D009277:Nandrolone; D007703:Peptidyl-Dipeptidase A; D000077603:Nandrolone Decanoate