Low dose of methyltestosterone in ovariectomised rats improves baroreflex sensitivity without geno‐ and cytotoxicity |
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Authors: | Ewelyne M. de Lima Andrews M. do Nascimento Girlandia A. Brasil Placielle F. Filete Ieda C. Kalil Dominik Lenz Denise C. Endringer Nazaré S. Bissoli Tadeu U. de Andrade |
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Affiliation: | 1. Department of Pharmaceutical Sciences, University Vila Velha, Vila Velha, Espirito Santo – ES, Brazil;2. Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória, Espirito Santo – ES, Brazil |
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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). |
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Keywords: | baroreflex Bezold– Jarisch reflex genotoxicity hormone replacement therapy methyltestosterone |
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