After a 7-day lead-in period, one of three beta-adrenergic antagomists was taken for 2 wk by 10 healthy male subjects. The drugs were metoprolol (cardioselective) and propranolol and nadolol (both nonselective). Dosage was according to currently recommended regimens and was increased after the first week (50 to100 mg b.i.d., 20 to 40 mg q.i.d., and 80 to 160 mg q.d.). Pulmonary mechanics and density dependence (DD) of maximal expiratory flow were measured before and at the end of the placebo lead-in period and the low- and high-dose treatment weeks. Total lung capacity (TLC), residual volume (RV), and RV/TLC all rose (P less than 0.05) after high-dose nadolol. Forced vital capacity (FVC) and expiratory reserve volume fell (P less than 0.05) after high-dose nadolol. Forced vital capacity (FVC) and expiratory reserve volume fell (P less than 0.05) after high-dose metoprolol. There was no change in forced expiratory volume in 1.0 sec (FEV1), FEV1/FVC, maximal midexpiratory flow rate, or airway resistance with any of the beta-antagonists. Decreases (P less than 0.05) in maximal expiratory flow determined at 50% of the vital capacity occurred after propranolol and metoprolol, but not after nadolol. A dose-related decrease in DD at 50% of the vital capacity accompanied nadolol dosing, but was significant only after the high-dose regimen. The decreases in DD with nadolol, as well as its effect on RV/TLC, are consistent with small airway narrowing. The findings with metoprolol and propranolol suggest that they affect central as well as peripheral airways.
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