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Abstract Title:

Neuroprotective effects of testosterone upon cardiac sympathetic function in rats with induced heart failure.

Abstract Source:

Eur J Pharmacol. 2009 Oct 1;619(1-3):68-74. Epub 2009 Aug 6. PMID: 19665014

Abstract Author(s):

Ying Han, Lu Fu, Weiju Sun, Junxian Cao, Rongsheng Xie, Ping Zhou, Ningning Kang, Junfeng Sun

Article Affiliation:

Department of Cardiovascular Medicine, First Affiliated Hospital, Harbin Medical University, Harbin 150001, China.

Abstract:

The current study was designed to determine whether castration with or without testosterone replacement resulted in changes in cardiac sympathetic nerve activity in rats with heart failure induced by isoproterenol. At eight weeks post-castration, dysfunction of the cardiac sympathetic nerve system was aggravated as indicated by elevated plasma norepinephrine, reduced myocardial norepinephrine content and tyrosine hydroxylase (TH) protein. These effects of castration were reversed by testosterone replacement, as indicated by decreased plasma norepinephrine, increased myocardial norepinephrine and density of TH-labeled nerve fibers, as well as by an upregulated expression of myocardial TH protein. We also explored whether the neuroprotective effect of testosterone was influenced by the antiandrogen, flutamide. Interestingly, flutamide failed to block these testosterone-induced neuroprotective effects on the cardiac sympathetic nervous system in castrated rats with heart failure. These results provide the first evidence that endogenous testosterone deprivation in rats significantly worsened cardiac sympathetic function during pathophysiological changes associated with heart failure, and testosterone replacement reversed these adverse effects. These neuroprotective effects of testosterone, may, in part, be mediated through an upregulation in TH protein, but do not appear to involve the androgen receptor. Therefore, androgens may play an important role in modulating pathophysiological changes in the cardiac sympathetic nervous system that result from heart failure and our findings suggest the potential for beneficial effects of testosterone in the treatment of this condition.

Study Type : Animal Study

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