title: Chronic clenbuterol treatment compromises force production without directly altering skeletal muscle contractile machinery.
abstract: Clenbuterol is a β2 -adrenergic receptor agonist known to induce skeletal muscle hypertrophy and a slow-to-fast phenotypic shift. The aim of the present study was to test the effects of chronic clenbuterol treatment on contractile efficiency and explore the underlying mechanisms, i.e. the muscle contractile machinery and calcium-handling ability. Forty-three 6-week-old male Wistar rats were randomly allocated to one of six groups that were treated with either subcutaneous equimolar doses of clenbuterol (4 mg kg(-1) day(-1) ) or saline solution for 9, 14 or 21 days. In addition to the muscle hypertrophy, although an 89% increase in absolute maximal tetanic force (Po ) was noted, specific maximal tetanic force (sPo) was unchanged or even depressed in the slow twitch muscle of the clenbuterol-treated rats (P < 0.05). The fit of muscle contraction and relaxation force kinetics indicated that clenbuterol treatment significantly reduced the rate constant of force development and the slow and fast rate constants of relaxation in extensor digitorum longus muscle (P < 0.05), and only the fast rate constant of relaxation in soleus muscle (P < 0.05). Myofibrillar ATPase activity increased in both relaxed and activated conditions in soleus (P < 0.001), suggesting that the depressed specific tension was not due to the myosin head alteration itself. Moreover, action potential-elicited Ca(2+) transients in flexor digitorum brevis fibres (fast twitch fibres) from clenbuterol-treated animals demonstrated decreased amplitude after 14 days (-19%, P < 0.01) and 21 days (-25%, P < 0.01). In conclusion, we showed that chronic clenbuterol treatment reduces contractile efficiency, with altered contraction and relaxation kinetics, but without directly altering the contractile machinery. Lower Ca(2+) release during contraction could partially explain these deleterious effects.
authors: Faculté des Sciences du Sport, Université Montpellier, 700 avenue du Pic Saint-Loup, F-34060, Montpellier, France; INRA, UMR866, Université Montpellier, 2 Place Viala, F-34060, Montpellier, France.
authors: G
authors: G
authors: Py
authors: C
authors: C
authors: Ramonatxo
authors: P
authors: P
authors: Sirvent
authors: A M J
authors: AM
authors: Sanchez
authors: A G
authors: AG
authors: Philippe
authors: A
authors: A
authors: Douillard
authors: O
authors: O
authors: Galbès
authors: C
authors: C
authors: Lionne
authors: A
authors: A
authors: Bonnieu
authors: A
authors: A
authors: Chopard
authors: O
authors: O
authors: Cazorla
authors: A
authors: A
authors: Lacampagne
authors: R B
authors: RB
authors: Candau
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002976:Clenbuterol / Q000494:pharmacology*; D006984:Hypertrophy / Q000139:chemically induced / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000318:Adrenergic beta-Agonists; D000251:Adenosine Triphosphatases; D002118:Calcium; D002976:Clenbuterol
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