Differential response of β‐adrenergic receptor—mediated heart rate and aortic blood flow acceleration to timolol

The apparent affinity of β-adrenergic receptors for timolol in the sinus node and ventricular myocardium was compared in 11 normal male subjects. Sinus nodal function was assessed by heart rate, and left ventricular systolic function was assessed by Doppler-derived aortic blood flow acceleration. The dose of isoproterenol required for a heart rate or acceleration increase of 35% (I35) was determined before and 2 hours after an oral 10 mg dose of timolol. The apparent affinity constant (ka) for timolol binding to the receptor was calculated from the serum timolol concentration and the ratio of the I35 after timolol/I35 before timolol. The I35 for sinus node and ventricular myocardium were not significantly different from one another. The ka for timolol binding to the sinus node (1.14 × 106 mol/L), however, was significantly greater (p < 0.05) than ka for ventricular myocardium (7.85 × 105 mol/L). These findings suggest that β-adrenergic receptors in the sinus node may have an overall greater affinity for β-blocking agents than do receptors in the ventricular myocardium. Clinical Pharmacology and Therapeutics (1992) 51, 296–301; doi:10.1038/clpt.1992.25