Selective regulation of β1‐and β2‐adrenoceptors in the human heart by chronic β‐adrenoceptor antagonist treatment

• Published in: British journal of pharmacology Vol. 94; no. 3; pp. 685 - 692
• Main Authors: Michel, M.C., Pingsmann, A., Beckeringh, J.J., Zerkowski, H.‐R., Doetsch, N., Brodde, O.‐E.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-07-1988; Nature Publishing
• Subjects: Biological and medical sciences; Cardiotonic agents; Cardiovascular system; Medical sciences; Pharmacology. Drug treatments; Heart; Human; Heart failure; Coronary artery; In vitro; Isolated organ; β-Adrenergic receptor; Biological fixation; Regulation(control); Heart disease; Mechanism of action; Lymphocyte; Right atrium; Beta blocking agent
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1988.tb11576.x

1
In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the β‐adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on β‐adrenoceptor density in right atria (containing 70% β1‐ and 30% β2‐adrenoceptors) and in lymphocytes (having only β2‐adrenoceptors) was studied.
2
β‐Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (−)−[125I]‐iodocyanopindolol (ICYP) binding; the relative amount of right atrial β‐ and β2‐adrenoceptors was determined by inhibition of ICYP binding by the selective β2‐adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND.
3
With the exception of pindolol, all β‐adrenoceptor antagonists increased right atrial β‐adrenoceptor density compared to that observed in atria from patients not treated with β‐adrenoceptor antagonists.
4
All β‐adrenoceptor antagonists increased right atrial β1‐adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial β2‐adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it.
5
Similarly, in corresponding lymphocytes, only sotalol or propranolol increased β2‐adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it.
6
It is concluded that β‐adrenoceptor antagonists subtype‐selectively regulate cardiac and lymphocyte β‐adrenoceptor subtypes. The selective increase in cardiac β1‐adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end‐stage congestive cardiomyopathy following intermittent treatment with low doses of selective β1‐adrenoceptor antagonists.