2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury

Beitzel, Felice, Paul Gregorevic, James G. Ryall, David R. Plant, Martin N. Sillence, and Gordon S. Lynch. 2-Adrenoceptor agonist fenoterol enhances functional repair of regenerating rat skeletal muscle after injury. J Appl Physiol 96: 1385–1392, 2004. First published November 7, 2003; 10.1152/japplphysiol.01081.2003.— 2-Adrenoceptor agonists such as fenoterol are anabolic in skeletal muscle, and because they promote hypertrophy and improve forceproducing capacity, they have potential application for enhancing muscle repair after injury. No previous studies have measured the 2-adrenoceptor population in regenerating skeletal muscle or determined whether fenoterol can improve functional recovery in regenerating muscle after 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, which 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 1 day ) or an equal volume of saline for 2, 7, 14, or 21 days. Radioligand binding assays identified a 3.5-fold increase in 2-adrenoceptor density in regenerating muscle at 2 days postinjury. Isometric contractile properties of rat EDL muscles were measured in vitro. At 14 and 21 days postinjury, maximum force production (Po) of injured muscles from fenoterol-treated rats was 19 and 18% greater than from saline-treated rats, respectively, indicating more rapid restoration of function after 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 2-adrenoceptor-mediated mechanisms in muscle regeneration and show clearly that fenoterol hastens recovery after injury, indicating its potential therapeutic application.