Beta adrenoreceptor subtype cross regulation in the human heart
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.