Effect of testosterone replacement therapy on cardiac performance and oxidative stress in orchidectomized rats

S. M. Eleawa, H. F. Sakr, A. M. Hussein, A. S. Assiri, N. M K Bayoumy, M. Alkhateeb

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Aim: To investigate the effects of testosterone on myocardial contractility, oxidative stress status and expression of sodium channel protein (Nav1.5) and inward rectifying K channels (Kir 2.x) in normal and orchidectomized (ORX) rats. Methods: One hundred four rats were randomly assigned into four groups (n = 26, each) as follows: (i) untreated controls, (ii) testosterone treated, (iii) orchidectomized rats and (iv) orchidectomized, testosterone-treated rats. Treatments with the vehicle or testosterone were carried out for 12 weeks, three times per week. At the end of treatment, surface ECG, isolated heart, tissue oxidative stress and lipid peroxidation experiments were carried out on the cardiac tissues. Also, immunohistochemical examination for Nav1.5 and PCR detection of mRNA of Kir2.1, Kir2.2 and Kir2.4 subunits of K channels were carried out. Results: Orchidectomy impaired cardiac contractile function parameters left ventricular developed pressure (LVDP) and the peaks of the positive and negative pressure derivatives (dP/dtmax and -dP/dtmax respectively), increased heart rate and prolonged QT and QTc intervals, elevated pro-oxidant state in rat's hearts and decreased the expression of Kir 2.1 but not Kir2.2, Kir 2.4 and Nav1.5 channels. Exogenous testosterone administration to orchidectomized rats restored heart contractility and shortened QT and QTc intervals to their normal values, ameliorated the generated pro-oxidant state and improved the expression of Nav1.5 and Kir2.1, but not Kir2.2 or Kir2.4 channels. Conclusion: Testosterone improved cardiac contractility and shortened QT and QTc intervals in ORX rats. An effect that might be dependent of reduction in oxidative stress and enhancement of Kir2.1 channels but independent of Nav1.5 channel protein.

Original languageEnglish
Pages (from-to)136-147
Number of pages12
JournalActa Physiologica
Volume209
Issue number2
DOIs
Publication statusPublished - Oct 2013

Keywords

  • Cardiac performance
  • Kir2.x channels
  • Nav1.5 channels
  • Orchidectomy
  • Oxidative stress
  • Testosterone

ASJC Scopus subject areas

  • Physiology

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