Abstract
The effects of the beta-adrenergic receptor antagonists carazolol, celiprolol, indenolol and propranolol on myocardial Mg(2+)-dependent, Na(+)- and K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase, EC 3.6.1.3) were compared with those of ouabain in guinea-pig heart preparations. All four drugs inhibited the enzyme activity in a concentration-dependent fashion similar to that shown by ouabain. Celiprolol exerted inhibitory actions (5-95%) in the concentration range of 0.5-3000 microM, while propranolol showed similar activity in the range of 100-4000 microM. Carazolol and indenolol exhibited intermediary effects. Their inhibitory effective ranges were 95-4000 and 10-5000 microM, respectively. The concentrations for half maximal inhibition of the enzyme activity were 0.74 +/- 0.12 mM for carazolol, 0.62 +/- 0.09 mM for celiprolol, 0.80 +/- 0.11 mM for indenolol and 1.03 +/- 0.19 mM for propranolol. Accordingly, the rank order of their potencies exhibited the following trend: celiprolol greater than carazolol greater than indenolol greater than propranolol. The present results show that these drugs exhibit inhibitory actions on the Na(+)-K(+)-ATPase activity, which may be suggested as a possible biochemical basis for their proarrhythmic effects.