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Research ArticleCARDIOVASCULAR

Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

Mahmoud M. El-Mas, Elham A. Afify, Amal G. Omar and Fouad M. Sharabi
Journal of Pharmacology and Experimental Therapeutics April 2002, 301 (1) 346-354; DOI: https://doi.org/10.1124/jpet.301.1.346
Mahmoud M. El-Mas
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Elham A. Afify
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Amal G. Omar
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Fouad M. Sharabi
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Abstract

Previous studies have shown that the immunosuppressant drug cyclosporine A attenuates arterial baroreceptor function. This study investigated whether the modulatory effect of cyclosporine on baroreceptor function involves inhibition of the baroreflex-facilitatory effect of testosterone. The role of cardiac autonomic control in cyclosporine-testosterone baroreflex interaction was also investigated. Baroreflex curves relating bradycardic responses to increments in blood pressure evoked by phenylephrine were constructed in conscious, sham-operated, castrated rats and in testosterone-replaced castrated (CAS + T) rats in the absence and presence of cyclosporine. The slopes of the curves were taken as an index of the baroreflex sensitivity (BRS). Short-term (11–13 days) cyclosporine treatment or castration reduced plasma testosterone levels and caused similar attenuation of the reflex bradycardia, as indicated by the significantly smaller BRS compared with sham-operated values (−0.97 ± 0.07, −0.86 ± 0.06, and −1.47 ± 0.10 beats/min/mm Hg, respectively). The notion that androgens facilitate baroreflexes is further confirmed by the observation that testosterone replacement of castrated rats restored plasma testosterone and BRS to sham-operated levels. Cyclosporine had no effect on BRS in castrated rats but caused a significant reduction in CAS + T rats. Muscarinic blockade by atropine caused approximately 60% reduction in the BRS in sham-operated rats, an effect that was significantly and similarly diminished by castration, cyclosporine, or their combination. β-Adrenergic blockade by propranolol caused no significant changes in BRS. These findings suggest that cyclosporine attenuates baroreflex responsiveness via, at least partly, inhibition of the testosterone-induced facilitation of cardiomotor vagal control.

Footnotes

  • Supported by the Faculty of Pharmacy, University of Alexandria, Egypt.

  • Abbreviations:
    HR
    heart rate
    BRS
    baroreflex sensitivity
    MAP
    mean arterial pressure
    CAS
    castrated
    CAS + T
    testosterone-replaced CAS
    CyA
    cyclosporine A-treated
    ANOVA
    analysis of variance
    • Received August 28, 2001.
    • Accepted December 18, 2001.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 301 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 1
1 Apr 2002
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Research ArticleCARDIOVASCULAR

Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

Mahmoud M. El-Mas, Elham A. Afify, Amal G. Omar and Fouad M. Sharabi
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 346-354; DOI: https://doi.org/10.1124/jpet.301.1.346

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Research ArticleCARDIOVASCULAR

Cyclosporine Adversely Affects Baroreflexes via Inhibition of Testosterone Modulation of Cardiac Vagal Control

Mahmoud M. El-Mas, Elham A. Afify, Amal G. Omar and Fouad M. Sharabi
Journal of Pharmacology and Experimental Therapeutics April 1, 2002, 301 (1) 346-354; DOI: https://doi.org/10.1124/jpet.301.1.346
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