At rest, plasma FFA levels were not significantly different in the three groups (Table 1). During exercise plasma FFA increased in SAL and β2+GLU but not in β2. After 23 min, plasma FFA levels were significantly lower in β2 than in SAL (P < 0.05).
Plasma glycerol concentration at rest did not differ among groups and increased during exercise in all groups (P < 0.01) (Table 1).
Plasma BCAA levels were not significantly different among the three groups at rest and during exercise (Table 1).
Decreased physical work capacity is commonly observed after the administration of β-blocking agents and is generally more pronounced during nonselective β1+2-blockade compared with selective β1-blockade (8,12,24,32,35). Only a few studies used selective β2-adrenoceptor blockade. In humans, Hespel et al. (19) observed a nonsignificant reduction in exercise duration after oral treatment with the selective β2-blocker ICI 118,551. In rats Trudeau et al. (34) found a marked reduction in running time to exhaustion during treadmill exercise, using the same drug, and this was confirmed in the present experiments using a similar experimental protocol. This reduced endurance work capacity may result from changes in ammonia metabolism since a rise in the blood ammonia concentration can lead to an increase in ammonia in critical regions of the brain with resulting central nervous dysfunction (central fatigue) (3,16,39). The reduction in running times observed in our rats under selective β2-blockade (23 ± 4.3 min compared to 44 ± 5.2 min with placebo) could therefore be caused by the very high blood ammonia levels (>140 μmol·L−1).
Surprisingly, time-to-exhaustion was not improved when glucose was supplemented during β2-blockade (26 ± 3.2 min in β2+glucose compared to 23 ± 4.3 min in β2), despite lower blood ammonia levels. However, the decreased exercise capacity in the presence of β-blockers may also be related to some other effects of β-blockade, such as a decreased oxygen transport to the contracting muscle (hemodynamic effects), the inhibition of other β2-mediated metabolic processes (lipolysis), or to effects of β-blockers not directly related to energy metabolism, such as changes in ionic equilibrium (35).
The authors are grateful to P. Hespel and W. Samyn for their expert technical assistance in muscle glycogen assessment (P.H.) and chemical analyses (W.S.), and to W. Eechaute for the statistical analysis.
1. Anthony, A. Review article: β3
-adrenoceptor agonists: future anti-inflammatory drugs for the gastrointestinal tract? Aliment. Pharmacol. Ther. 10:859–863, 1996.
2. Arner, P., E. Kriegholm, P. Engfeldt, and J. Bolinder. Adrenergic regulation of lipolysis in situ
at rest and during exercise. J. Clin. Invest. 85:893–898, 1990.
3. Banister, E. W. and B. J. C. Cameron. Exercise-induced hyperammonemia: peripheral and central effects. Int. J. Sports Med. 11:S129-S142, 1990.
4. Bilski, A., S. Dorries, J. D. Fitzgerald, R. Jessup, H. Tucker, and J. Wale. ICI 118,551, a potent β2
adrenoreceptor antagonist. Br. J. Pharmacol. 69:292P-293P, 1980.
5. Broberg, S., A. Katz, and K. Sahlin. Propranolol enhances adenine nucleotide degradation in human muscle during exercise. J. Appl. Physiol. 65:2478–2483, 1988.
6. Broberg, S. and K. Sahlin. Hyperammonemia during prolonged repeated submaximal exercise: an effect of glycogen depletion. J. Appl. Physiol. 65:2475–2477, 1988.
7. Chasiotis, D., R. Brandt, R. C. Harris, and E. Hultman. Effects of beta-blockade on glycogen metabolism in human subjects during exercise. Am. J. Physiol. 245:E166-E170, 1983.
8. Cleroux, J., P. Van Nguyen, A. W. Taylor, and F. H. N. Leenen. Effects of β1
- vs. β1
-blockade on exercise endurance and muscle metabolism in humans. J. Appl. Physiol. 66:548–554, 1989.
9. Costill, D. L., E. Coyle, G. Dalsky, W. Evans, W. Fink, and D. Hoopes. Effects of elevated plasma FFA and insulin on muscle glycogen usage during exercise. J. Appl. Physiol. 43:695–699, 1977.
10. Czarnowski, D., J. Langfort, W. Pilis, and J. Gorski. Effect of low-carbohydrate diet on plasma and sweat ammonia
concentrations during prolonged nonexhausting exercise. Eur. J. Appl. Physiol. 70:70–74, 1995.
11. Delp, M. D. and C. Duan. Composition and size of type I, IIA, IID/X, and IIB fibers and citrate synthase activity of rat muscle. J. Appl. Physiol. 80:261–270, 1996.
12. Gollnick, P. D., R. G. Soule, A. W. Taylor, C. Williams, and C. D. Iannuzzo. Exercise induced glycogenolysis and lipolysis in the rat: hormonal influence. Am. J. Physiol. 219:729–733, 1970.
13. Gorski, J. and K. Pietrzyk. The effect of beta-adrenergic receptor blockade on intramuscular glycogen mobilization during exercise in the rat. Eur. J. Appl. Physiol. 48:201–205, 1982.
14. Greenhaff, P. L., J. B. Leiper, D. Ball, and R. J. Maughan. The influence of dietary manipulation on plasma ammonia
accumulation during incremental exercise in man. Eur. J. Appl. Physiol. 63:338–344, 1991.
15. Gullestad, L., L. Dolva, E. Søyland, and J. Kjekshus. Difference between beta-1 selective and nonselective beta-blockade during continuous and intermittent exercise. Clin. Physiol. 8:487–499, 1988.
16. Guezennec, C. Y., A. Abdelmalki, B. Serrurier, et al. Effects of prolonged exercise on brain ammonia
and amino acids. Int. J. Sports Med. 19:323–327, 1998.
17. Hall, P. E., S. R. Smith, and M. J. Kendall. The effects of four β-adrenoreceptor antagonists during modest exercise on plasma ammonia
and heart rate. Clin. Sci. 72:679–682, 1987.
18. Hargreaves, M. and E. A. Richter. Regulation of skeletal muscle glycogenolysis during exercise. Can. J. Sport Sci. 13:197–203, 1988.
19. Hespel, P., P. Lijnen, L. Vanhees, et al. Differentiation of exercise-induced metabolic responses during selective β1
antagonism. Med. Sci. Sports Exerc. 18:186–191, 1986.
20. Hespel, P. and E. A. Richter. Mechanism linking glycogen concentration and glycogenolytic rate in perfused contracting rat skeletal muscle. Biochem. J. 284:777–780, 1992.
21. Juhlin-Dannfelt, A. C., S. E. Terblanche, R. D. Fell, J. C. Young, and J. O. Holloszy. Effects of beta-adrenoreceptor blockade on glycogenolysis during exercise. J. Appl. Physiol. 53:549–554, 1982.
22. Lamont, L., A. J. McCullough, and S. C. Kalhan. β-Adrenergic blockade heightens the exercise-induced increase in leucine oxidation. Am. J. Physiol. 268 (Endocrinol Metab 31):E910-E916, 1995.
23. Liggett, S. B., S. D. Shah, and P. E. Cryer. Characterization of β-adrenergic receptors of human skeletal muscle obtained by needle biopsy. Am. J. Physiol. 254 (Endocrinol. Metab. 17):E795-E798, 1988.
24. Lundborg P., H. Aström, C. Bengtsson, et al. Effect of β-adrenoreceptor blockade on exercise performance and metabolism. Clin. Sci. 61:299–305, 1981.
25. Marmy-Conus, N., S. Fabris, J. Proietto, and M. Hargreaves. Pre-exercise glucose ingestion and glucose kinetics during exercise. J. Appl. Physiol. 81:853–857, 1996.
26. Matthys, D., P. Calders, and J. L. Pannier. Effects of acute nonselective beta-adrenergic blockade on plasma ammonia
levels in exercising dogs. Int. J. Sports Med. 16:373–377, 1995.
27. Matthys, D., P. Calders, J. Kint, and J. L. Pannier. Effects of acute cardioselective and nonselective beta-adrenergic blockade on plasma ammonia
levels in exercising dogs. Arch. Physiol. Biochem. 104:14–19, 1996.
28. Matthys, D., P. Calders, and J. L. Pannier. Inhaled salbutamol decreases blood ammonia
levels during exercise in normal subjects. Eur. J. Appl. Physiol. 79:110–113, 1998.
29. Mineo, I., N. Kono, Y. Yamada, et al. Glucose infusion abolishes the excessive ATP degradation in working muscles of a patient with McArdle’s disease. Muscle Nerve 13:618–620, 1990.
30. Roeykens, J., L. Magnus, R. Rogers, R. Meeusen, and K. De Meirleir. Blood ammonia
: heart rate relationship during graded exercise is not influenced by glycogen depletion. Int. J. Sports Med. 19:26–31, 1998.
31. Spencer, M. K. and A. Katz. Role of glycogen in control of glycolysis and IMP formation in human muscle during exercise. Am. J. Physiol. 260 (Endocrinol Metab 23):E859-E864, 1991.
32. Stankiewicz-Choroszucha, B. and J. Gorski. Effect of decreased availability of substrates on intramuscular triglyceride utilization during exercise. Eur. J. Appl. Physiol. 40:27–35, 1978.
33. Strosberg, A. D. Structure and function of the β3
-adrenergic receptor. Annu. Rev. Pharmacol. Toxicol. 37:421–450, 1997.
34. Trudeau, F., F. Péronnet, L. Béliveau, and G. Brisson. Metabolic and endocrine responses to prolonged exercise in rats under β2
-adrenergic blockade. Can. J. Physiol. Pharmacol. 67:192–196, 1989.
35. Van Baak, M. A. Beta-adrenoreceptor blockade and exercise: an update. Sports Med. 4:209–225, 1988.
36. Van Baak, M. A. and J. M. V. Mooij. Effect of glucose infusion on endurance performance
after β-adrenoreceptor blocker administration. J. Appl. Physiol. 77:641–646, 1994.
37. Wagenmakers, A. J. M., J. H. Coakley, and R. H. T. Edwards. Metabolism of branched-chain amino acids and ammonia
during exercise: clues from McArdle’s disease. Int. J. Sports Med. 11:S101-S113, 1990.
38. Wagenmakers, A. J. M., E. Beckers, F. Brouns, et al. Carbohydrate supplementation, glycogen depletion, and amino acid metabolism during exercise. Am. J. Physiol. 260:E883-E890, 1991.
39. Wagenmakers, A. J. M. Role of amino acids and ammonia
in mechanisms of fatigue
. In: Muscle Fatigue
Mechanisms in Exercise and Training, Med Sport Sci. Marconnet, Vol. 34, P. V. Komi, B. Saltin, and O. M. Sejersted (Eds.). Basel: Karger, 1992, pp. 69–86.
40. Wilson C., S. Wilson, V. Piercy, M. V. Sennitt, and J. R. S. Arch. The rat lipolytic β-adrenoceptor: studies using novel β-adrenoceptor agonists. Eur. J. Pharmacol. 100:309–319, 1984.