Changes in the density of beta adrenergic receptors in rat lymphocytes, heart and lung after chronic treatment with propranolol.

Abrupt withdrawal after the chronic administration of propranolol results in clinical syndromes that suggest adrenergic hypersensitivity. Furthermore, propranolol administration has been shown to lead to an increase in the density of beta adrenergic receptors on human lymphocytes. The present studies were designed to assess the relevance of changes measured in lymphocytes to changes that may occur in solid tissues. Direct measurement of the density and properties of beta adrenergic receptors in membrane fragments was performed in vitro using the radioligand [125I]iodohydroxybenzylpindolol. Chronic infusion of propranolol by s.c. implanted osmotic minipumps generated sustained plasma concentrations of propranolol sufficient to cause chronic blockade of beta adrenergic receptors. Infusion of propranolol for 7 days resulted in significant increases in the density of beta adrenergic receptors in rat ventricles, lungs and lymphocytes. A computer-assisted graphic analysis of results obtained in studies with drugs selective for beta-1 or beta-2 receptors revealed increases in the densities of both beta-1 an beta-2 adrenergic receptors. These results are consistent with the hypothesis that change in beta adrenergic receptors on lymphocytes are qualitatively similar to alterations in beta adrenergic receptors in solid tissues not routinely accessible in humans. Increases in the densities of beta-1 and/or beta-2 adrenergic receptors in solid tissues may be related to some of the untoward effects observed in humans after abrupt discontinuation of propranolol administration.