In support of cardiac chronotropic beta 2 adrenoceptors

The effects of atenolol (50 mg) and propranolol (40 mg) on exercise- and isoproterenol-induced heart rate increments were studied in 9 male volunteers. Propranolol reduced maximal heart rate from 187 +/- 4 to 146 +/- 7 beats/min and atenolol reduced it to 138 +/- 6 beats/min. There was no difference between the drugs at any point during exercise. Isoproterenol sensitivity was measured as the dose of isoproterenol required to increase resting heart rate by 25 beats/min (CD-25). Propranolol increased the CD-25 from 1.8 +/- 0.3 micrograms after placebo to 39 +/- 8 micrograms and atenolol increased the CD-25 to 8 +/- 2 micrograms. The increase by propranolol was significantly greater than that of atenolol. Intravenous atropine (0.04 mg/kg) did not alter the isoproterenol CD-25 during placebo or atenolol. The CD-25 with propranolol decreased after atropine (39 +/- 8 versus 25 +/- 5 micrograms) and was due to diminished plasma propranolol concentrations as the drug sensitivity (measured by Ka) was unchanged before (12 +/- 2 ml/ng) and after (10 +/- 3 ml/ng) atropine. These data support the hypothesis that moderate exercise is primarily a beta 1-mediated response and therefore equally antagonized by cardioselective and nonselective blockers, but that isoproterenol stimulates both beta 1 and beta 2 receptors. The greater ability of the nonselective agent to antagonize isoproterenol tachycardia with no significant change after atropine suggests the presence of cardiac beta 2 chronotropic receptors. The physiologic and pathologic importance of these receptors has yet to be determined.