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Differential response of β‐adrenergic receptor—mediated heart rate and aortic blood flow acceleration to timolol
Author(s) -
Clifton G Dennis,
Chandler Mary H H,
Pennell Andrew T,
McCoy Randall A,
Harrison Michael R
Publication year - 1992
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1992.25
Subject(s) - timolol , medicine , heart rate , cardiology , receptor , endocrinology , chemistry , blood pressure , surgery , intraocular pressure
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% (I 35 ) was determined before and 2 hours after an oral 10 mg dose of timolol. The apparent affinity constant (k a ) for timolol binding to the receptor was calculated from the serum timolol concentration and the ratio of the I 35 after timolol/I 35 before timolol. The I 35 for sinus node and ventricular myocardium were not significantly different from one another. The k a for timolol binding to the sinus node (1.14 × 10 6 mol/L), however, was significantly greater ( p < 0.05) than k a for ventricular myocardium (7.85 × 10 5 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