THE EFFECT OF β-BLOCKADE ON PLASMA POTASSIUM AND MAGNESIUM HOMEOSTASIS DURING EXERCISE

Abstract

Drug-induced changes in plasma potassium (K) and magnesium (Mg) homeostasis during physical exercise are important because hypokalemia and hypomagnesemia may increase the risk of cardiac arrhythmias. Because β-blocking drugs reduce mortality in coronary heart disease, counteract the hypokalemic action of epinephrine, and potentiate exercise-induced hyperkalemia, we administered orally 50 mg atenolol, 10 mg pindolol, and 80 mg propranolol to 15 healthy volunteers in a randomized, double-blind, placebo-controlled crossover study and monitored heart rate, plasma K, Mg, norepinephrine, epinephrine, and the extent to which the drugs occupied rabbit lung β-receptors and rat reticulocyte β-receptors in the circulating plasma during a bicycle exercise test (duration of 30 min, work load of 100 W). The drug-induced increases in plasma K and Mg varied between 22% and 23%, and 4% and 6%, respectively. Pindolol reduced heart rate least and atenolol most (p < 0.05). All three agents potentiated norepinephrine response to exercise (p < 0.01). Only propranolol potentiated epinephrine response significantly (p <0.01). Because the mean β and β occupancy of atenolol 75.4 (6.4)% and 10.7 (3.6)%, mean (SD) significantly differed from those of pindolol 98.7 (0.4)% and 98.4 (0.5)% (mean [SD]) and propranolol 85.9 (5.4)% and 96.5 (1.3)% (mean [SD]), the differences in the receptor occupancy did not affect plasma K and Mg responses to exercise. The β-occupancy predicted the reduction of heart rate with an average Pearson correlation coefficient (r) of 0.89–0.96. In conclusion, differences in the β- and β- receptor binding between drugs do not markedly affect plasma K and Mg levels during physical exercise. These responses are, however, attenuated by the agonist activity of pindolol which may unfavorably affect its antiarrhyth-mic properties.