RELATIONSHIP BETWEEN POTASSIUM CONCENTRATION AND INHIBITORY EFFECTS OF BETA-ADRENERGIC BLOCKERS ON MYOCARDIAL NA+, K+-ATPASE

The inhibitory effects of propranolol, carazolol and metoprolol on the Mg2+-dependent ATP hydrolytic action of myocardial Na+, K+-ATPase were tested in guinea-pig heart preparations in media containing different K+ concentrations, in order to investigate their potential relevance to the cardiac effects of these agents. All 3 drugs exhibited concentration-dependent inhibitory actions on enzyme activity at potassium ion concentrations of 2.5, 5 and 10 mmol/L; IC50 (concentrations producing 50% inhibition) values at these concentrations were 0.53 +/- 0.06, 0.72 +/- 0.04 and 1.90 +/- 0.25 mmol/L for carazolol, 0.79 +/- 0.04, 0.86 +/- 0.07 and 0.96 +/- 0.09 mmol/L for metoprolol, and 0.98 +/- 0.04, 1.55 +/- 0.11 and 3.65 +/- 0.37 mmol/L for propranolol. Thus, reducing the K+ concentration from the physiological level of 5 mmol/L to 2.5 mmol/L produced a significant increase in the inhibitory potencies of these drugs: while increasing the K+ concentration to 10 mmol/L resulted in a decrease in inhibitory potencies. This relationship between K+ concentration and inhibitory effects of beta-adrenergic receptor antagonists may have some relevance to the proarrhythmic effects of these drugs.