Zhou H H, Silberstein D J, Koshakji R P, Wood A J
Division of Clinical Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Clin Pharmacol Ther. 1989 Jun;45(6):587-92. doi: 10.1038/clpt.1989.78.
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 less than 0.05; 60 mg/day: r = 0.5279, p less than 0.05; 120 mg/day: r = 0.5888, p less than 0.01; 240 mg/day: r = 0.6783, p less than 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 less than 0.001; 60 mg/day: r = 0.7218, p less than 0.002; 120 mg/day: r = 0.7814, p less than 0.001; 240 mg/day: r = 0.6899, p less than 0.005). We conclude that the density of beta-adrenergic receptors is one of the principal factors that control beta-receptor response to antagonists in human beings.
为了确定受体密度变化以及对β-肾上腺素能拮抗剂反应中个体间显著差异的作用，我们测定了16名健康受试者中普萘洛尔产生的β受体阻滞与β-肾上腺素能受体密度（Bmax）之间的关系，这些受试者在每个剂量水平下每8小时接受10、20、40和80mg普萘洛尔，共1天。产生的β受体阻滞程度通过运动性心动过速的降低来评估。β受体阻滞程度与治疗前淋巴细胞Bmax相关（30mg/天：r = 0.6290，p < 0.05；60mg/天：r = 0.5279，p < 0.05；120mg/天：r = 0.5888，p < 0.01；240mg/天：r = 0.6783，p < 0.005）。当根据血浆普萘洛尔浓度校正β受体阻滞程度时，相关性进一步提高（30mg/天：r = 0.7636，p < 0.001；60mg/天：r = 0.7218，p < 0.002；120mg/天：r = 0.7814，p < 0.001；240mg/天：r = 0.6899，p < 0.005）。我们得出结论，β-肾上腺素能受体密度是控制人类β受体对拮抗剂反应的主要因素之一。
