In vivo demonstration of cardiac β2-adrenoreceptor sensitization by β1-antagonist treatment

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Abstract

Treatment with β1-selective antagonists causes selective sensitization of isolated strips of human atrial myocardium to the inotropic action of epinephrine and β2-agonists but not of norepinephrine. To determine whether β1-selective antagonist treatment alters the responsiveness of cardiac β2-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 β-blockers. The mean dose required to cause an increase in heart rate of 30 beats/min was 2.29 μg (log dose 0.36±0.12 μg [mean±SEM]) in the atenolol-treated patients. In the non-β-blocker-treated patients, the dose required to cause an increase in heart rate of 30 beats/min was significantly greater, 8.91 μg (log dose 0.95±0.11 μg) (p<0.005). We conclude that treatment with β1-selective β-blockers leads to increased cardiac responsiveness to β2-adrenoreceptor stimulation. This may be the underlying mechanism of the β-blocker withdrawal syndrome and may make the heart more susceptible to the adverse effects of epinephrine in situations of stress (e.g., myocardial infarction).

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Hall, J. A., Petch, M. C., & Brown, M. J. (1991). In vivo demonstration of cardiac β2-adrenoreceptor sensitization by β1-antagonist treatment. Circulation Research, 69(4), 959–964. https://doi.org/10.1161/01.RES.69.4.959

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