A B S T R A C T Abrupt withdrawal after the chronic administration of propranolol has resulted in clinical syndromes that suggest adrenergic hypersensitivity. The effect of propranolol administration and withdrawal on ,-adrenergic receptors was studied in human lymphocyte membranes. Receptor density was quantitated by direct binding assays with the radioligand [1251]iodohydroxybenzylpindolol. Administration ofpropranolol (160 mg/d) for 8 d resulted in trough plasma levels of -35 ng/ml. By day 5 ofpropranolol administration the density of /3-adrenergic receptors had increased 43+4% (P < 0.01) above pretreatment levels. Abrupt withdrawal of propranolol was followed by the disappearance of propranolol from the plasma within 24 h. The density of f3-adrenergic receptors did not return to pretreatment level for several days. Physiologic supersensitivity of 8-adrenergic receptor-mediated responses was suggested by the appearance of significant increases in the orthostatic change in heart rate (P < 0.05) and the orthostatic change in the heart rate-systolic blood pressure product (P < 0.01) during the first 48 h after propranolol withdrawal. These data show that propranolol administration leads to an increase in the density of f3-adrenergic receptors in human tissue. The results are consistent with the hypothesis that some of the untoward effects observed after abrupt discontinuation of propranolol are caused by 8-receptor-mediated adrenergic hypersensitivity.

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