Does bisoprolol cause selective beta 2 adrenoreceptor sensitisation in healthy volunteers?
Treatment with a beta-1 blocker leads to sensitization of cardiac beta-2 adrenoreceptors, a previously unrecognized cross-sensitization that may diminish antiarrhythmic efficacy.
OBJECTIVES: To find out in a prospective study whether beta 1 blocker treatment causes selective beta 2 adrenoreceptor sensitisation, and to find whether such sensitisation is confined to the heart. DESIGN: A placebo controlled cross over study of two weeks of selective beta 1 blocker treatment with 10 mg of bisoprolol daily. SUBJECTS: Six healthy volunteers. OUTCOME MEASURES: Three days after stopping the 10 mg of bisoprolol or placebo, subjects underwent treadmill exercise (to measure cardiac beta 1 receptor responsiveness) and were given salbutamol injections (to measure cardiac beta 2 receptor responsiveness). Secondary end points were the responses of serum potassium, glucose, and insulin to beta 2 stimulation. RESULTS: There was no difference in exercise induced increases in heart rate, but after treatment with bisoprolol the dose of salbutamol required to increase heart rate by 40 beats/min was 1.9 micrograms/kg compared with 2.9 micrograms/kg after placebo (p < 0.005). The fall in diastolic blood pressure was not significantly different on the two occasions. Hypokalaemia induced by salbutamol, but not hyperglycaemia or hyperinsulinaemia, was enhanced after bisoprolol. CONCLUSION: This study shows that treatment with a beta 1 blocker in vivo leads to sensitisation of cardiac beta 2 adrenoreceptors but not cardiac beta 1 adrenoreceptors or vascular beta 2 receptors. This previously unrecognised form of receptor cross sensitisation in the heart may noticeably diminish the efficacy of selective beta 1 blockade in preventing arrhythmias in patients with ischaemic heart disease. These findings reopen the question of which type of beta blocker is more appropriate for such patients.
Hall et al. (Thu,) studied this question.