In order to study the regulation of human cardiac and vascular β-adrenoceptors as induced by β-adrenoceptor antagonism we determined β-adrenoceptor density and subtype distribution in right atria, saphenous veins and lymphocytes from 60 patients undergoing coronary artery bypass grafting; 42 of these patients were chronically treated with different β-adrenoceptor antagonists [without intrinsic sympathomimetic activity: propranolol, sotalol (non-selective); metoprolol, atenolol (β1-selective); with intrinsic sympathomimetic activity: pindolol (non-selective)] and 18 patients not treated with β-adrenoceptor antagonists were taken as controls. In the right atria (70% β1-, 30% β2-adrenoceptors) of all groups except the pindolol group, total β-adrenoceptor density was higher than in controls. A more detailed analysis revealed that all β-adrenoceptor antagonists increased right atrial β1-adrenoceptor density, but right atrial β2-adrenoceptor density was increased only in the sotalol/propranolol group, remaining unchanged in the metoprolol and atenolol groups, and was decreased in the pindolol group. Similarly, in saphenous veins and circulating lymphocytes (in both, the β-adrenoceptors were almost exclusively β2-adrenoceptors), only propranolol/sotalol increased the β2-adrenoceptor density, while metoprolol or atenolol did not affect it. Moreover, in the pindolol group lymphocyte β2-adrenoceptor density was decreased. It is concluded that in man all β-adrenoceptor antagonists without intrinsic sympathomimetic activity increase cardiac and vascular β-adrenoceptor density, but in a subtype-selective manner. Accordingly, pindolol can be subclassified as a partial β2-adrenoceptor agonist.
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