Metabolic effects of beta2-agonists in relation to exercise performance

Beta2-agonists are frequently used in the treatment of asthma and exercise-induced bronchoconstriction in elite athletes. However, aside from a bronchodilatory effect, beta2-agonists have also been shown to improve exercise performance, which makes these substances subjected to misuse by elite athletes. The present PhD thesis is based on four manuscripts in which the acute effects of beta2-agonists on exercise performance were investigated. The aims were 1) to investigate whether supratherapeutic inhalation of beta2-agonists enhances muscle strength, anaerobic performance and aerobic performance, 2) to uncover the mechanisms behind potential beta2-adrenergic improvements in anaerobic performance, 3) to investigate whether inhalation of beta2-agonists is ergogenic in elite athletes with or without airway hyperresponsiveness (AHR). Results from the studies of the thesis show that supratherapeutic inhalation of beta2-agonists increases muscle strength and improves performance during maximal sprinting lasting up to ~ 60 s, whereas no effect was observed on exercise lasting more than ~ 180 s.
The ergogenic effects of beta2-agonists on power output during maximal sprinting requires administration of a certain dose, but a further increase in dose does not seem to elicit a greater performance-enhancing effect. Moreover, the effects of beta2-agonists on performance are unaffected by training status and AHR, but athletes with AHR who regularly use beta2-agonists get a reduced
ergogenic response presumably due to receptor down-regulation. The mechanisms behind beta2-adrenergic increases in power output during maximal sprinting should be attributed to various factors. During maximal sprinting lasting 10-30 s, it is evident that beta2-drenergic increases in glycogenolysis
and glycolysis counteract breakdown of ATP, which may delay fatigue development by reducing accumulation of AMP, Pi, Mg2+. The increased glycogenolysis and glycolysis may primarily counteract breakdown of ATP and development of fatigue in type II fibers. In addition, the increase in power
output observed during maximal sprinting following administration of beta2-agonists is most likely associated with greater and more frequent Ca2+ transients presumably due to an increased release of Ca2+ from the sarcoplasmic reticulum (SR). Through a PKA-dependent phosphorylation of FXYD1, the Na+-K+ ATPase may contribute to this greater release of Ca2+ from the SR by counteracting accumulation of interstitial K+ and thereby loss of membrane excitability.