Chronic β1‐adrenoceptor antagonist treatment sensitizes β2‐adrenoceptors, but desensitizes M2‐muscarinic receptors in the human right atrium

• Published in: British journal of pharmacology Vol. 101; no. 2; pp. 363 - 369
• Main Authors: Motomura, S., Deighton, N.M., Zerkowski, H.‐R., Doetsch, N., Michel, M.C., Brodde, O.‐E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.1990
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1990.tb12715.x

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 β1‐adrenoceptor function, but desensitizes muscarinic M2‐receptor function in the human heart.