Orchiectomy or androgen receptor blockade attenuates baroreflex-mediated bradycardia in conscious rats.
BACKGROUND
Previous studies have shown that testosterone enhances baroreflex bradycardia. Therefore, conscious unrestrained rats were used to investigate the role of the androgen receptor in the testosterone-mediated modulation of baroreflex bradycardia. Androgen depletion (3 weeks), and androgen receptor blockade (20-24 h), were implemented to test the hypothesis that testosterone influences baroreflex bradycardia via its activity at the androgen receptor in male rats. Phenylephrine (1-16 microg kg(-1)) was used to assess baroreflex bradycardia.


RESULTS
Androgen depletion attenuated baroreflex bradycardia (P < 0.01). The antiandrogen flutamide (5, 15, or 30 mg kg(-1), s.c.) caused dose-related attenuation of baroreflex bradycardia in spite of a significant (P < 0.05) increase in serum testosterone. The latter did not lead to increased serum 17beta-estradiol level.


CONCLUSIONS
The data suggest: 1) Androgen depletion or adequate androgen receptor blockade attenuates baroreflex bradycardia. 2) The reflex increase in serum testosterone may counterbalance the action of the lower doses (5 or 15 mg kg(-1)) of flutamide. 3) The absence of a change in serum 17beta-estradiol rules out its contribution to flutamide action on baroreflex bradycardia.
Ward
Gregg R
GR
Department of Pharmacology, The Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA.
Abdel-Rahman
Abdel A
AA
Department of Pharmacology, The Brody School of Medicine at East Carolina University, Greenville, NC, 27858, USA.
D000726:Androgen Antagonists / Q000009:adverse effects / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001919:Bradycardia / Q000139:chemically induced / Q000503:physiopathology*; D003243:Consciousness / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000502:physiology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D011944:Receptors, Androgen