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J Appl Physiol (November 7, 2003). doi:10.1152/japplphysiol.01081.2003
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Submitted on October 6, 2003
Accepted on November 4, 2003

{beta}2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle following injury

Felice Beitzel1, Paul Gregorevic1, James G Ryall1, David R Plant1, Martin N Sillence2, and Gordon S Lynch1*

1 Physiology, The University of Melbourne, Melbourne, Victoria, Australia
2 Agriculture, Charles Sturt University, Wagga Wagga, New South Wales, Australia

* To whom correspondence should be addressed. E-mail: gsl{at}unimelb.edu.au.

{beta}2-Adrenoceptor agonists such as fenoterol, are anabolic in skeletal muscle and because they promote hypertrophy and improve force-producing capacity, they have potential application for enhancing muscle repair following injury. No previous studies have measured the {beta}2-adrenoceptor population in regenerating skeletal muscle or determined whether fenoterol can improve functional recovery in regenerating muscle following myotoxic injury. In the present study, the extensor digitorum longus (EDL) muscle of the right hindlimb of deeply anesthetized rats was injected with bupivacaine hydrochloride, that caused complete degeneration of all muscle fibers. The EDL muscle of the left hindlimb served as the uninjured control. Rats received either fenoterol (1.4 mg/kg/day) or an equal volume of saline for 2, 7, 14 or 21 days. Radioligand binding assays identified a ~3.5-fold increase in {beta}2-adrenoceptor density in regenerating muscle at 2 days post-injury. Isometric contractile properties of rat EDL muscles were measured in vitro. At 14 and 21 days post-injury, maximum force production (Po) of injured muscles from fenoterol-treated rats was 19% and 18% greater than in saline-treated rats, respectively, indicating more rapid restoration of function following injury. The increase in Po in fenoterol-treated rats was due to increases in muscle mass, fiber cross sectional area, and protein content. These findings suggest a physiological role for {beta}2-adrenoceptor mediated mechanisms in muscle regeneration, and show clearly that fenoterol hastens recovery following injury, indicating its potential therapeutic application.




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