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Five days were allowed between successive drug administrations and the order of drug administration was randomized. Heart rate, arterial pressure, oxygen consumption, minute ventilation and CO2 production were monitored. Plasma drug concentrations were measured at the time of exercise. Judged'by plasma levels, propranolol was about three times more potent than metoprolol in attenuating heart rate. Both drugs produced a wide variation in plasma levels after a given oral dose, and both'drugs attenuated the systolic blood pressure response to exercise. Neither drug affected diastolic blood pressure or maximum oxygen consumption, maximum minute ventilation or the anae'robic threshold. We conclude that there is no evidence that the cardioselective drug metoprolol is superior to propranolol in terms of the ability to perform or respond to short-term maximal exercise. In addition, the fact that maximal oxygen consumption and the anaerobic threshold were unaffected implies that fatigue during exercise while on g-adrenergic blocking drugs is'not due to an effect of these drugs in limiting blood flow to the exercising extremities.THE f3-ADRENERGIC blocking drugs propranolol and metoprolol are used widely in the treatment of patients with hypertension, ischemic heart disease and a variety of other conditions. Metoprolol is cardioFrom the Divisions of Cardiology and Clinical Pharmacology,

SUMMARY High levels of ,B-adrenergic stimulation accompany strenuous exercise, but the possibility that #-adrenergic blockade might prevent exercise conditioning has not been adequately investigated. We studied normal, sedentary men, ages 21-35 years, before and after 5 weeks of intensive aerobic conditioning. On a double-blind protocol, eight received placebo and nine propranolol throughout the conditioning period. A high level of ,B-adrenergic blockade was documented in all subjects receiving propranolol; individual mean plasma propranolol concentrations were 100-292 ng/ml. Both groups trained at comparable intensities. Graded maximal treadmill tests were performed before starting drugs or training, and were repeated 3-5 days after completing the conditioning period, when ,B-adrenergic blockade was no longer present. In subjects who received placebo, training increased exercise duration (16.4 ± 1.3 to 21.2 ± 1.5 minutes [± SEMI, p < 0.01) and maximal oxygen uptake (43.6 ± 2.9 to 52.7 ± 3.2 ml/kg/min, p < 0.05). Subjects who received propranolol had only modest improvement in exercise duration (16.0 ± 0.6 to 17.3 i 0.9 minutes, p < 0.05), and no significant change in maximal oxygen uptake (40.4 ± 1.4 to 40.9 i 0.9 ml/kg/min). With training, diastolic pressure at maximal exercise decreased in subjects who received placebo (63 ± 3 to 48 ± 3 mm Hg,p < 0.05) but was unchanged in subjects who received propranolol. Training did not alter maximal heart rate in either group. Thus, high levels of f3-adrenergic blockade markedly attenuated aerobic conditioning in these normal subjects. We conclude that ,B-adrenergic stimulation is essential in exercise conditioning.ENDURANCE EXERCISE results in adaptive changes in the cardiovascular system known as training or conditioning effects. In normal subjects performing near-maximal exercise, the conditioning process results in greater physical work capacity, total body oxygen consumption, cardiac output, stroke volume and arteriovenous oxygen difference.1 ' At submaximal work loads, conditioning results in diminished myocardial oxygen consumption, lower heart rate and higher stroke volume.2 S Similar changes occur with exercise training in many patients with coronary artery disease.4 6-11 The potentially favorable nature of these changes is the physiologic basis for the use of aerobic exercise programs in rehabilitating patients with coronary artery disease. coronary artery disease, and aerobic exercise is often prescribed in cardiac rehabilitation programs. If ,B-adrenergic stimulation is needed for exercise conditioning, then fi blockade might be expected to interfere with this process. To test this hypothesis, we studied 17 healthy, sedentary men before, during and after an intensive 5-week aerobic exercise program. Using a double-blind protocol, eight subjects received placebo and nine propranolol during the training period. Conditioning effects were compared in the two groups by evaluating maximal treadmill performance while the subjects were not taking drugs before and aft...