INVIVO DEMONSTRATION OF CARDIAC BETA-2-ADRENOCEPTOR SENSITIZATION BY BETA-1-ANTAGONIST TREATMENT

Treatment with beta-1-selective antagonists causes selective sensitization of isolated strips of human atrial myocardium to the inotropic action of epinephrine and beta-2-agonists but not of norepinephrine. To determine whether beta-1-selective antagonist treatment alters the responsiveness of cardiac beta-2-adrenoreceptors in vivo, we measured the positive chronotropic responses to salbutamol injected into the right coronary artery. Ten patients treated with atenolol (50-100 mg daily) were compared with 10 patients not treated with beta-blockers. The mean dose required to cause an increase in heart rate of 30 beats/min was 2.29-mu-g (log dose 0.36 +/- 0.12-mu-g [mean +/- SEM]) in the atenolol-treated patients. In the non-beta-blocker-treated patients, the dose required to cause an increase in heart rate of 30 beats/min was significantly greater, 8.91-mu-g (log dose 0.95 +/- 0.11-mu-g) (p < 0.005). We conclude that treatment with beta-1-selective beta-blockers leads to increased cardiac responsiveness to beta-2-adrenoreceptor stimulation. This may be the underlying mechanism of the beta-blocker withdrawal syndrome and may make the heart more susceptible to the adverse effects of epinephrine in situations of stress (e.g., myocardial infarction).