Carbohydrate availability affects ammonemia during exercise after 2-adrenergic blockade

MATTHYS, DIRK; DERAVE, WIM; CALDERS, PATRICK; PANNIER, JEAN-LOUIS

Medicine & Science in Sports & Exercise:
BASIC SCIENCES: Original Investigations
Abstract

MATTHYS, D., W. DERAVE, P. CALDERS, and J.-L. PANNIER. Carbohydrate availability affects ammonemia during exercise after β2-adrenergic blockade. Med. Sci. Sports Exerc., Vol. 32, No. 5, pp. 940–945, 2000.

Purpose: β-Adrenergic blockade increases blood ammonia concentration during exercise. The purpose of this study was to assess the role of decreased carbohydrate availability in this process.

Methods: Wistar rats (N = 47) were injected intravenously with a selective β2-adrenoceptor blocker (ICI 118,551), placebo, or β2-blocker + glucose 1 h before a treadmill exercise test. Blood samples were taken to measure the concentration of ammonia, glucose, lactic acid, free fatty acids (FFA), glycerol, branched-chain amino acids (BCAA), and muscle samples for determination of glycogen content.

Results: β2-adrenergic blockade shortened running time to exhaustion (23 ± 4.3 min compared to 44 ± 5.2 min with placebo), increased blood ammonia levels (146.7 ± 16.21 μmol·L−1 compared to 47.5 ± 0.92 μmol·L−1 with placebo) and prevented exercise-induced glycogen breakdown in soleus and gastrocnemius muscles. Pre-exercise supplementation of glucose during β2-blockade restored exercise-induced glycogen breakdown and reduced blood ammonia concentration during exercise (66.5 ± 5.65 mmol·L−1) but did not improve exercise capacity (26 ± 3.2 min) when compared with β2-blockade alone.

Conclusion: The results suggest that the enhanced rise in blood ammonia concentration during exercise after β-blockade is caused by impaired carbohydrate availability.

The mechanisms responsible for the reduction in exercise capacity in the presence of β-blockers have not yet been elucidated, but they may be related to their metabolic effects (35). The administration of β-blocking drugs has an effect on the metabolism of lipids, carbohydrates, and ammonia during exercise. β-blocker administration has been reported to inhibit exercise-induced lipolysis, which leads to reduced availability of fatty acids (2,8,12,15,24,32). The effect of β-blockade on muscle glycogen utilization is more controversial, but at least in some experimental conditions β-blockade was shown to inhibit muscle glycogenolysis during exercise (34). The reduction in exercise capacity in the presence of β-adrenergic blockers may therefore be related to a reduction in the availability of substrates for energy metabolism in skeletal muscle (24).

Furthermore, β-adrenergic blockade is known to increase the blood ammonia concentration during exercise (5,17,26,27), and hyperammonemia has been associated with fatigue during prolonged exercise (3). In addition, previous studies have shown that the accumulation of blood ammonia during exercise is increased in conditions of reduced carbohydrate availability (6,10,14,30,37,38).

The aim of the present study was to investigate whether the exercise-induced hyperammonemia after β-blockade is related to decreased carbohydrate availability, e.g., because of impaired glycogenolysis. In view of the fact that the exercise-induced hyperammonemia is more pronounced after the administration of nonselective β1+2-blockers than after cardioselective β1-blockers (17,27) and that skeletal muscle adrenoreceptors are mainly of the β2-type (23), we used a selective β2-adrenoceptor antagonist (ICI 118,551) in the present study. Experiments were done with and without supplementation of glucose in addition to the β-adrenergic blockade, to investigate the effects of improved carbohydrate availability during β-blockade.

Author Information

Department of Pediatric Cardiology, Institute of Kinesiology and Sport Sciences, and Laboratory of Normal and Pathological Physiology, University of Ghent, B-9000 Ghent, BELGIUM

Submitted for publication October 1998.

Accepted for publication June 1999.

Address for correspondence: D. Matthys, M.D., Department of Pediatric Cardiology, University Hospital, De Pintelaan 186, B-9000 Ghent, Belgium. E-mail: dirk.matthys@rug.ac.be.

©2000The American College of Sports Medicine