CHRONIC BETA-1-ADRENOCEPTOR ANTAGONIST TREATMENT SENSITIZES BETA-2-ADRENOCEPTORS, BUT DESENSITIZES M2-MUSCARINIC RECEPTORS IN THE HUMAN RIGHT ATRIUM

1. In 64 patients undergoing coronary artery bypass grafting the effects of chronic β1-adrenoceptor antagonist (metoprolol, atenolol, bisoprolol) treatment on right atrial β-adrenoceptor and muscarinic M2-receptor number and functional responsiveness were investigated. 2. The β1-adrenoceptor antagonists increased right atrial β1-adrenoceptor number, did not affect β2-adrenoceptor number, and decreased muscarinic M2-receptor number. 3. Concomitantly, activation of right atrial adenylate cyclase by 10 μM, GTP, 10 μM isoprenaline and 1 μM forskolin was enhanced and inhibition by 100 μM carbachol was diminished. 4. On isolated, electrically driven right atria the β1-adrenoceptor-mediated positive inotropic effect of noradrenaline was - even with β1-adrenoceptor number increased - not altered, while the β2-adrenoceptor-mediated effect of procaterol was markedly enhanced. However, the carbachol-induced negative inotropic effect was decreased. 5. It is concluded that chronic β1-adrenoceptor antagonist treatment increases β1-adrenoceptor number and concomitantly sensitizes β2-adrenoceptor function, but desensitizes muscarinic M2-receptor function in the human heart.