Evidence for cardiac β2-adrenoceptors in man

Abstract

The effects of single doses of 50 mg atenolol (cardioselective), 40 mg propranolol (nonselective) and placebo on both exercise- and isoproterenol-induced tachycardia were compared in 2 experiments involving 9 normal subjects. Maximal exercise heart rate was reduced from 187 .+-. 4 (SEM [standard error of the mean]) after placebo to 146 .+-. 7 bpm [beats/min] after atenolol and 138 .+-. 6 bpm after propranolol, but there were no differences between the drugs. The effects on isoproterenol tachycardia were determined before and after atropine (0.04 mg/kg i.v.). Isoproterenol sensitivity was determined as the i.v. dose that increased heart rate by 25 bpm (CD25) and this was increased from 1.8 .+-. 0.3 .mu.g after placebo to 38.9 .+-. 8.3 .mu.g after propranolol and 8.3 .+-. 1.7 .mu.g after atenolol. The difference in the effects of the two was significant. After atropine the CD25 was unchanged after placebo (2.3 .+-. 0.3 .mu.g) and atenolol (7.7 .+-. 1.3 .mu.g); it was reduced after propranolol (24.8 .+-. 5.0 .mu.g), but remained different from atenolol. This change with propranolol was associated with a fall in plasma concentrations during the experiment but, when propranolol sensitivity was calculated as the apparent Ka, this was unchanged by atropine (11.7 .+-. 2.1 and 10.1 .+-. 2.5 ml/ng). Exercise-induced tachycardia evidently results largely from .beta.1-receptor activation that is blocked by both cardioselective and nonselective drugs, whereas isoproterenol activates both .beta.1- and .beta.2-receptors so that after cardioselective blockade there remains a .beta.2-component that can be blocked with a nonselective drug. While there appear to be .beta.2-receptors in the human heart, their physiologic or pathologic roles remain to be defined.