Adaptational responses to prolonged beta-adrenoceptor blockade in adult rabbits.

1 A method for measuring propranolol concentrations in plasma has been modified to permit estimations to be made on small volumes. The method has been used to correlate blockade of heart rate increases in response to intravenous isoprenaline, in both young and adult rabbits, with plasma concentrations of propranolol after subcutaneous injections of 2 or 4 mg/kg. It has been found that the relation between beta-adrenoceptor blockade and plasma concentrations is the same in rabbits as that determined by previous workers in man. 2 Adult Dutch dwarf rabbits were treated for 9 weeks twice daily subcutaneously with 2 mg/kg propranolol, or 10 mg/kg practolol, or with saline. 3 The treatment caused no change in heart weight in relation to body weight or in the water content of the hearts, in contrast to effects previously observed in young rabbits. 4 As in the young rabbits, treatment did cause a prolongation of action potential duration, as measured with intracellular electrodes in hearts of animals killed 24 h after the last dose of drug. 5 In another series of experiments, with a similar regime of treatment for 6 weeks, a significant reduction of diastolic blood pressure was observed in the propranolol group. 6 During the course of treatment and at the end, there was no change in the heart-rate increases observed in response to intravenous isoprenaline administered not less than 15 h after the previous dose of beta-blockers. Thus no functional alteration in sensitivity ot beta-adrenoceptor stimulation was apparent.