Testosterone improves cardiac function and alters angiotensin II receptors in isoproterenol-induced heart failure

Arch Cardiovasc Dis. 2012 Feb;105(2):68-76. doi: 10.1016/j.acvd.2011.12.002. Epub 2012 Feb 11.

Abstract

Background: The renin-angiotensin-aldosterone system is known to play an important role in the pathophysiology and development of heart failure. Several studies have reported the benefits of testosterone in heart failure. However, the mechanisms of testosterone-induced effects on heart failure require further study.

Aims: To determine the effects of castration and testosterone administration on cardiac function and angiotensin II receptor function in rats with isoproterenol-induced heart failure.

Methods: Wistar rats were divided randomly into control and heart failure groups. The heart failure groups were further divided into the following groups: castration; castration+testosterone replacement; and sham castration. Echocardiography and haemodynamic measurements were used to evaluate cardiac function. Cardiocyte apoptosis and fibrosis were determined using terminal deoxyribonucleotide transferase-mediated dUTP nick-end labelling (TUNEL) staining and Masson's Trichrome staining, respectively. Angiotensin II receptor (AT1 and AT2) messenger ribonucleic acid (mRNA) expression levels were assayed using real-time reverse transcriptase-polymerase chain reactions, while Western immunoblotting was used to estimate Bcl-2 protein expression levels.

Results: Castration significantly increased cardiomyocyte apoptosis and fibrosis that was normally induced by isoproterenol (P<0.05). AT2 receptor mRNA expression in the castration group was increased and Bcl-2 protein expression was decreased compared with the castration+testosterone replacement group (P<0.05).

Conclusion: These data suggest that androgen therapy could play an important role in pathophysiological changes in heart failure and have beneficial effects for its treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blotting, Western
  • Disease Models, Animal
  • Fibrosis
  • Heart Failure / chemically induced
  • Heart Failure / diagnostic imaging
  • Heart Failure / drug therapy*
  • Heart Failure / metabolism
  • Heart Failure / pathology
  • Heart Failure / physiopathology
  • Hemodynamics / drug effects
  • Hormone Replacement Therapy*
  • In Situ Nick-End Labeling
  • Isoproterenol*
  • Male
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Orchiectomy
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptor, Angiotensin, Type 1 / drug effects
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptor, Angiotensin, Type 2 / drug effects*
  • Receptor, Angiotensin, Type 2 / genetics
  • Receptor, Angiotensin, Type 2 / metabolism
  • Recovery of Function
  • Renin-Angiotensin System / drug effects*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Testosterone Propionate / pharmacology*
  • Ultrasonography
  • Ventricular Function, Left / drug effects

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptor, Angiotensin, Type 2
  • Isoproterenol
  • Testosterone Propionate