Effects of beta blocking agents on the density of beta adrenoceptors and adenylate cyclase response in human myocardium: intrinsic sympathomimetic activity favours receptor upregulation

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Abstract
The density of beta adrenoceptors, the relative number of beta1 and beta2 adrenoceptor subtypes, and adenylate cyclase activity were studied in preparations from atrial biopsy specimens of 32 patients with coronary heart disease. Six patients were not receiving beta blocking agents, whereas the others were treated with different beta blocking drugs (timolol, propranolol, pindolol, metoprolol, and atenolol). Clinical and haemodynamic variables were similar in the different groups of patients. Beta adrenoceptor density was 17% significantly lower in the non-treated group than in the groups treated with beta blocking drugs. Among these, the group treated with pindolol, a drug with intrinsic sympathomimetic activity, had receptor densities that were 38% significantly higher than those treated with other beta blocking drugs and 51% significantly higher than the non-treated group. The relative numbers of beta1 and beta2 adrenoceptor subtypes were very similar in the different groups (beta, receptors 75-80%, beta2 receptors 20-25%). A significant increase in the ratios of terbutaline stimulated to basal and terbutaline stimulated to isoproterenol stimulated adenylate cyclase activities was found in patients treated with beta1 selective blockers (metoprolol, atenolol), indicating that beta1 selective drugs may improve beta2 receptor-adenylate cyclase coupling. In contrast, pindolol caused a significant reduction in the ratio of terbutaline stimulated to isoproterenol stimulated adenylate cyclase activity, indicating that this drug may cause a reduction in beta2 receptor-adenylate cyclase coupling efficacy. Thus treatment with beta blocking agents causes upregulation of human myocardial beta receptor density. Intrinsic sympathomimetic activity seems to favour receptor upregulation. Treatment with beta, selective and non-selective drugs does not affect the relative concentration of beta receptor subtypes. Efficacy of beta2 receptor-adenylate cyclase coupling appears to be changed in different directions by different drug regimens.