EXERCISE METABOLISM IN HEALTHY-VOLUNTEERS TAKING ATENOLOL, HIGH AND LOW-DOSES OF METOPROLOL CR Z0K, AND PLACEBO/

1 Exercise and beta-adrenoceptor blockade have important roles in the prevention and treatment of cardiovascular disease, but fatigue and a reduced capacity to exercise are commonly reported side effects of bet a-adrenoceptor blockers. The reduced capacity to exercise may be partl y caused by a reduction in fat metabolism. 2 We investigated the effec ts of atenolol 50 mg, metoprolol CR/Z0K 50 mg, metoprolol CR/Z0K 100 m g and placebo, on heart rate, energy expenditure, fat oxidation, plasm a free fatty acids, glycerol, glucose, lactate, ammonia and perceived exertion during 2 h of treadmill walking at 40% of maximal oxygen upta ke in 20 healthy volunteers. 3 Compared with placebo (38.0%), total fa t oxidation was significantly lower on atenolol 50 mg (30.1%) and meto prolol CR/Z0K 100 mg (31.0%), but not on metoprolol CR/Z0K 50 mg (33.7 %). Reductions in fat oxidation correlated well (r(2) = 0.970) with re ductions in exercising heart rate, and probably reflected the degree o f beta(1)-adrenoceptor blockade. Maximum plasma ammonia concentration was reached after 45 min of exercise on atenolol, 60 min on metoprolol CR/Z0K 100, and 75 min on metoprolol CR/Z0K 50, and was higher than p lacebo on all active drug treatments. 4. The greater reduction in fat oxidation with atenolol may be a reflection of a peak in plasma concen tration, which is avoided with a controlled release preparation.