In vivo demonstration of cardiac beta 2-adrenoreceptor 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 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).
Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge, UK.
J A
JA
Hall
M C
MC
Petch
M J
MJ
Brown
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D001262:Atenolol / Q000494:pharmacology; D003331:Coronary Vessels; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007267:Injections; D008297:Male; D008875:Middle Aged; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000319:Adrenergic beta-Antagonists; D011943:Receptors, Adrenergic, beta; D001262:Atenolol; D000420:Albuterol