Evaluation of β-Adrenerglc Blocking Agents in Presence of Adrenergic Tone

Abstract

The importance of the level of adrenergic tone in the determination of the dose–response curve to noradrenaline (NA) and in the evaluation of β-adrenergic blocking agents was studied in open-chest sodium pentobarbital anesthetized dogs by injecting drugs directly into the sinus node artery. Changes in the level of adrenergic tone by stimulating the right stellate ganglion resulted in variation of the observed chronotropic response to NA and of its ED50. The chronotropic responses were corrected by taking into account the underlying adrenergic tone. The negative chronotropic effect of dl-propranolol (1 and 10 μg) appeared to be related to its β-blocking properties and not to its quinidine-like effects as shown by the lack of effect of d-propranolol injected at the same doses. The magnitude of the negative chronotropic effects of 10 μg of propranolol and 100 μg of practolol, oxprenolol, and sotalol was shown to be related to the initial heart rate and consequently to the level of adrenergic tone. The comparison of these four β-blocking agents was carried out on corrected dose-response curves to NA. Their relative potencies were found to be: propranolol > oxprenolol > practolol > sotalol, corresponding to ratios of 1, [Formula: see text], [Formula: see text], and [Formula: see text]