Time couse of the blockade effect of propranolol on sinus node and atrioventricular node

The time course of the blockade effect of propranolol on the sinus node (SN) and the atrioventricular node (AVN) was studied in six normal volunteers. Serial isoproterenol infusions were done before and after oral propranolol administration, 160 mg daily for two days. The inhibition by propranolol of the heart rate increases due to isoproterenol was used to assess the blockade of the sinus node, and the diminution by propranolol of the shortening in the PR interval due to isoproterenol was used to assess the blockade of the atrioventricular node. The blockade effects on the sinus node and the atrioventricular node were identical and persisted more than 24 hours. There was no good relationship between plasma propranolol and blockade effect on sinus node and/or atrioventricular node as propranolol was no longer detectable in the plasma 24 hours after the last dose. A transient hypersensitivity to isoproterenol was present 36 to 48 hours after propranolol withdrawal. The explanation of these phenomena most likely lies in the peculiar nature of beta-adrenergic receptors.