title: Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno- and cytotoxicity.
abstract: This study evaluated the effects of the isolated use of a low dose of methyltestosterone (MT) on cardiovascular reflexes and hormonal levels and its geno- and cytotoxic safety in ovariectomized rats. Female Wistar rats were divided into four groups (n = 6), respectively: SHAM (received vehicle methylcellulose 0.5%), SHAM + MT (received MT 0.05 mg/kg), OVX (received vehicle), and OVX + MT (received MT). Twenty-one days after ovariectomy, treatment was given orally daily for 28 days. The Bezold-Jarisch reflex (BJR) was analyzed by measuring the bradycardic and hypotensive responses elicited by phenylbiguanide (PBG) administration. The baroreflex sensitivity (BRS) was evaluated by phenylephrine and sodium nitroprussite. Myocyte hypertrophy was determined by morphometric analysis of H&E stained slides. Biochemical data were analyzed, as well as micronucleus assay. MT improved BRS and increased testosterone values, but did not change estradiol in the OVX group. MT did not promote changes in mean arterial pressure, heart rate, BJR, serum concentrations of troponin I, weight and histopathology of the heart. MT was able to restore the BRS in OVX rats. The geno- and cytotoxic safety of the MT was demonstrated by the absence of an increase in the micronucleus (PCEMN) or change in the ratio between normochromatic erythrocytes and polychromatic erythrocytes (NCE/PCE).
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Denise G
authors.initials: DG
authors.lastname: Terra
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Ewelyne M
authors.initials: EM
authors.lastname: de Lima
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Av. Marechal Campos, n°1468, Vitória, Espirito Santo - ES, CEP 29042-755, Brazil.
authors.forename: Andrews M
authors.initials: AM
authors.lastname: do Nascimento
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Av. Marechal Campos, n°1468, Vitória, Espirito Santo - ES, CEP 29042-755, Brazil.
authors.forename: Girlandia A
authors.initials: GA
authors.lastname: Brasil
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Placielle F
authors.initials: PF
authors.lastname: Filete
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Ieda C
authors.initials: IC
authors.lastname: Kalil
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Dominik
authors.initials: D
authors.lastname: Lenz
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Denise C
authors.initials: DC
authors.lastname: Endringer
authors.affiliation: Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Av. Marechal Campos, n°1468, Vitória, Espirito Santo - ES, CEP 29042-755, Brazil.
authors.forename: Nazaré S
authors.initials: NS
authors.lastname: Bissoli
authors.affiliation: Department of Pharmaceutical Sciences, University Vila Velha, Av. Comissário José Dantas de Melo, n°21, Boa Vista, Vila Velha, Espirito Santo - ES, CEP 29102-920, Brazil.
authors.forename: Tadeu U
authors.initials: TU
authors.lastname: de Andrade
mesh_terms: D000818:Animals; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology*; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D005260:Female; D008777:Methyltestosterone / Q000008:administration & dosage* / Q000633:toxicity; D009152:Mutagenicity Tests / Q000379:methods; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar
chemical_list: D008777:Methyltestosterone
keywords: Bezold-Jarisch reflex; baroreflex; genotoxicity; hormone replacement therapy; methyltestosterone