Functional, cellular and molecular changes induced in the rat plantaris muscle by a low, non‐myotoxic dose of the β 2 ‐agonist clenbuterol

Abstract

Administration of β2-adrenergic receptor agonists, such as clenbuterol, has been proposed as an intervention against muscle wasting. However, large doses (mg.kg−1) of clenbuterol increase muscle growth and induce myocyte death. Here we investigate the effects of the non-myotoxic dose of 10 μg.kg−1of clenbuterol. Infusion of clenbuterol for 2 wk induced significant (P<0.05) protein accretion (17 %) and myofibre hypertrophy (20 %). The net power output of the plantaris, measured in situ using the oscillatory work loop technique, increased 21 % (P<0.05) but the muscle’s resistance to fatigue was significantly (P<0.05) diminished. The myofibre profile and oxidative capacity of the muscles of clenbuterol-treated animals were not altered substantially. However, differential analysis of the sarcoplasmic proteins, separated using 2D gel electrophoresis, revealed 16 protein spots that had significantly (P<0.05) changed. Peptide mass fingerprinting identified 6 of these protein spots, 3 (heat shock 72, β-enolase and glyceraldehyde-3-phosphate dehydrogenase) of which increased and 3 (aldolase A, phosphogylcerate mutase and adenylate kinase) decreased in response to clenbuterol. The likely explanation for the reduction in fatigue resistance was the decrease in adenylate kinase. Thus, any beneficial anabolic effects induced even by small therapeutic doses of clenbuterol need to be reconciled against a reduction in fatigue resistance.