Interindividual differences in β-receptor density contribute to variability in response to β-adrenoceptor antagonists

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Abstract
To determine the role of changes in receptor density and the considerable interindividual variability in the response to .beta.-adrenergic antagonists, we determined the relationship between the .beta.-blockade produced by propranolol and the .beta.-adrenergic receptor density (Bmax) in 16 healthy subjects who received 10, 20, 40, and 80 mg propranolol every 8 hours for 1 day at each dosage level. The extent of .beta.-blockade produced was assessed as the reduction in exercise tachycardia. The extent of .beta.-blockade correlated with pretreatment lymphocyte Bmax (30 mg/day: r = 0.6290, p < 0.05; 60 mg/day: r = 0.5279, p < 0.05; 120 mg/day: r = 0.5888, p < 0.01; 240 mg/day: r = 0.6783, p < 0.005). When the extent of .beta.-blockade was corrected for plasma propranolol concentrations, the correlation was further improved (30 mg/day: r = 0.7636, p < 0.001; 60 mg/day: r = 0.7218, p < 0.002; 120 mg/day: r = 0.7814, p < 0.001; 240 mg/day: r = 0.6899, p < 0.005). We conclude that the density of .beta.-adrenergic receptors in one of the principal factors that control .beta.-receptor repsonse to antagonists in human beings.