• L Gullestad, J Hallen, J I Medbø, O Grønnerød, I Holme, and O M Sejersted.
• Medical Department B, National Hospital of Norway, Oslo.
• Br J Clin Pharmacol. 1996 Jan 1;41(1):57-67.

Abstract1. Variable results have been reported on the effect of beta-adrenoceptor blockers on maximal oxygen uptake (VO2 max) and exercise endurance. This may in part be due to different subject populations, but it could also be due to an adaption of metabolic and haemodynamic responses to exercise during chronic treatment with beta-adrenoceptor blockers. The present study was therefore carried out to examine the effect of acute and chronic administration of the non-selective beta-adrenoceptor blocker propranolol on both peak VO2 and exercise performance in the same subjects. Since the effect of beta-adrenoceptor blockade has not been properly investigated in women, eight healthy women were compared with seven men. Progressive bicycle exercise to exhaustion was performed after propranolol 0.15 mg kg-1 i.v. (acute) or 80 mg three times daily for 2 weeks (chronic) or placebo given according to a double-blind crossover design. 2. Mean (s.e. mean) peak VO2, was significantly reduced from 42.3 (1.6) ml min-1 kg-1 during placebo to 40.3 (1.2, P < 0.05) ml min-1 kg-1 after acute and 39.1 (1.2, P < 0.001) ml min-1 kg-1 after chronic propranolol treatment. No significant difference in peak VO2 between the two propranolol treatment regimens was observed (mean difference 1.2, 95% CI -0.1 to 2.4 ml min-1 kg-1). There was no treatment interaction with gender. 3. Cumulative work, 163 (9.3) kJ, was significantly reduced by acute, 148 (7.7, P < 0.001) kJ, and chronic, 147 (7.6, P < 0.001) kJ, administration of propranolol since the time to exhaustion was reduced by 5.3% and 5.3%, respectively. There was no significant difference between the two regimens of propranolol (mean difference 0.2, 95% CI -6.7 to 7.0 kJ) or between the sexes. Maximal knee extensor and handgrip strengths were not affected by propranolol. 4. Whereas sex did not influence ventilatory, haemodynamic or metabolic parameters, some differences were observed between acute and chronic propranolol treatment. During submaximal exercise oxygen uptake was reduced by approximately 2% and RER values increased by 0.04-0.05 after chronic treatment in contrast to no effect of acute propranolol treatment. Heart rate and systolic blood pressure were reduced significantly more after chronic compared with acute propranolol treatment; peak heart rate being 186 (2.2), 147 (2.3) and 134 (2.3) beats min-1, and peak systolic blood pressure being 189 (7), 171 (4) and 161 (4) mmHg after placebo, acute and chronic propranolol administration, respectively. Also the exercise induced rise in potassium and lactate levels were modified differentially; the rise in potassium concentration was less after chronic compared with acute propranolol treatment and lactate levels were reduced only after chronic administration of propranolol. In contrast, ventilation, which was unchanged after propranolol during submaximal exercise, was reduced to similar extent at exhaustion from 108 (6.4) to 97 (7.2) and 96 (5.9) l min-1 after acute and chronic propranolol administration, respectively. Diastolic blood pressure and subjective perception of fatigue were similar across the treatment regimens. 5. The study has demonstrated that acute and chronic administration of propranolol result in different haemodynamic and metabolic response to exercise, although endurance and peak oxygen consumption were reduced to the same extent. The response to propranolol was not significantly different between men and women.

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