Cardiac beta-adrenoceptor modulation by amiodarone.

beta-Antiadrenergic properties are part of the pharmacological characteristics of amiodarone. In the present study, the action of amiodarone on rat-heart beta-adrenoceptors was investigated. [125I]Cyanopindolol (CYP) was used to label beta-adrenoceptors in crude rat-heart microsomes. In competition binding experiments, amiodarone up to 10(-6) M did not displace [125I]CYP from cardiac beta-adrenergic receptors. The effects of amiodarone on the number and affinity for [125I]CYP of beta-adrenoceptors were evaluated in saturation experiments. In vitro exposure of cardiac microsomes to 10(-5) M amiodarone did not modify these parameters. At higher concentrations the beta-receptor number decreased while the affinity for [125I]CYP was not affected. In vivo experiments showed a significant decrease in beta-adrenoceptor density after a single oral dose of 50 mg/kg amiodarone. In chronically treated animals, the same decrease in beta-receptor number was observed 24 hr after the last administration of the drug. 5'-Nucleotidase activity, another specific marker of the plasma membrane, was unaffected by the treatment. These results suggest that part of the beta-adrenergic antagonism of amiodarone is due to a decrease in the beta-adrenoceptor density at the surface of the myocardial cell.