title: Cyclosporine adversely affects baroreflexes via inhibition of testosterone modulation of cardiac vagal control.
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. beta-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.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Alexandria, Alexandria, Egypt. mahelm@hotmail.com
authors.forename: Mahmoud M
authors.initials: MM
authors.lastname: El-Mas
authors.forename: Elham A
authors.initials: EA
authors.lastname: Afify
authors.forename: Amal G
authors.initials: AG
authors.lastname: Omar
authors.forename: Fouad M
authors.initials: FM
authors.lastname: Sharabi
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009919:Orchiectomy; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013739:Testosterone / Q000037:antagonists & inhibitors*; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D007166:Immunosuppressive Agents; D018727:Muscarinic Antagonists; D010656:Phenylephrine; D013739:Testosterone; D001285:Atropine; D016572:Cyclosporine; D011433:Propranolol