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In vivo demonstration of cardiac beta 2-adrenoreceptor sensitization by beta 1-antagonist treatment
Abstract:
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 micrograms (log dose 0.36 +/- 0.12 micrograms [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 micrograms (log dose 0.95 +/- 0.11 micrograms) (p less than 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).
Insights
Beta 1-selective beta-blockers increase heart sensitivity to beta 2-adrenoreceptor stimulation. This may explain the beta-blocker withdrawal syndrome and increase cardiac risk during stress.
Area of Science:
- Cardiology
- Pharmacology
Background:
- Beta 1-selective antagonists can sensitize atrial myocardium to beta 2-agonists in vitro.
- The in vivo effect of beta 1-selective antagonists on cardiac beta 2-adrenoreceptor responsiveness remains unclear.
Purpose of the Study:
- To investigate whether beta 1-selective antagonist treatment alters cardiac beta 2-adrenoreceptor responsiveness in vivo.
Main Methods:
- Assessed positive chronotropic responses to salbutamol in 10 patients treated with atenolol and 10 control patients.
- Measured heart rate changes after right coronary artery injection of salbutamol.
Main Results:
- Atenolol-treated patients required significantly lower doses of salbutamol to increase heart rate by 30 beats/min (0.36 log micrograms) compared to controls (0.95 log micrograms).
- This indicates increased cardiac responsiveness to beta 2-adrenoreceptor stimulation after atenolol treatment.
Conclusions:
- Treatment with beta 1-selective beta-blockers enhances cardiac responsiveness to beta 2-adrenoreceptor stimulation.
- This sensitization may contribute to the beta-blocker withdrawal syndrome and increase cardiac vulnerability during stress events like myocardial infarction.