title: Long-term clenbuterol administration alters the isometric contractile properties of skeletal muscle from normal and dystrophin-deficient mdx mice.
abstract: 1. This study was designed to establish whether long-term treatment with the powerful anabolic agent clenbuterol has beneficial effects on dystrophin-deficient skeletal muscle function. 2. Normal (C57BL/10) and dystrophic (mdx) mice were administered clenbuterol (2 mg/kg per day) for 15 weeks. At 20 weeks of age, the extensor digitorum longus (EDL) and soleus muscles were removed, and their contractile and histochemical properties analysed. 3. Absolute and relative muscle masses were larger (P < 0.001) in mdx compared to C57BL/10 mice. These larger muscles produced larger absolute forces (P < 0.01) in the soleus of mdx mice compared to normal mice. Relative tetanic force was also larger (P < 0.05) in the soleus of mdx mice. In contrast, the absolute tetanic tension of the EDL was reduced (P < 0.01) in mdx mice compared to C57BL/10 mice, and both relative twitch and tetanic tensions were also lower (P < 0.001) in mdx mice. 4. Clenbuterol increased the lean muscle mass in both normal (10%, P < 0.05 and 20%, P < 0.01 for the EDL and soleus, respectively) and dystrophic (7%, P < 0.05 and 11%, P < 0.01) groups. Twitch contraction times were significantly faster in both the EDL (P < 0.001) and soleus (P < 0.01) muscles following clenbuterol administration, supported by fibre-type transitions towards fast-twitch fibres. Relative force levels of the soleus muscle of both C57BL/10 (40%, P < 0.01) and mdx (20%, P < 0.01) mice were increased significantly following clenbuterol treatment. No changes in the absolute or relative forces of the EDL muscles were observed in response to clenbuterol administration. 5. Clenbuterol was thus able to increase the force output of a slow-twitch, mixed (hence human-like) muscle but not fast-twitch muscle from mdx mice. The results lend tentative support to the potential role of clenbuterol as an anabolic agent in the treatment of muscle wasting diseases.
authors.affiliation: Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Hayes
authors.forename: D A
authors.initials: DA
authors.lastname: Williams
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology*; D016189:Dystrophin / Q000172:deficiency; D006321:Heart / Q000187:drug effects; D006651:Histocytochemistry; D007537:Isometric Contraction / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009137:Muscular Dystrophy, Animal / Q000473:pathology / Q000503:physiopathology*; D009929:Organ Size / Q000187:drug effects
chemical_list: D016189:Dystrophin; D002976:Clenbuterol