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Inhibition of β-adrenergic signalling impairs functional repair of rat skeletal muscle after injury

F. Beitzel,1 M.N. Sillence2 and G.S. Lynch,1 1Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Victoria 3010, Australia and 2School of Agriculture, Charles Sturt University, Wagga Wagga, New South Wales 2678, Australia.

β-adrenoceptor (β-AR) mediated signalling plays an important role in muscle regeneration, by altering the β-AR population and adenylate cyclase activity, to enhance cAMP production that promotes protein accretion. The aim was to block β-AR after muscle injury, to assess the importance of β-AR signalling in regeneration. Adult rats were anaesthetised (ketamine 100 mg/kg and xylazine 10 mg/kg, i.p.), and the EDL and soleus muscles of the right hindlimb injected with bupivacaine to cause complete destruction of all fibres. Rats received twice daily injections of the β2-selective antagonist, ICI-118551 (12.5 mg/kg, i.p.), the nonspecific β1- and β2-antagonist, propranolol (12.5mg/kg, i.p.), or saline, commencing 2 days prior to injury and continuing for 14 days post-injury. Rats were anaesthetised (as described above) for excision of isolated muscles and then killed by cardiac excision. Maximum force (Po) of injured EDL muscles from saline-treated rats was restored to 59% of control values, compared to only 50% and 53% of controls for ICI- and propranolol-treated rats, respectively. For injured soleus muscles from saline-treated rats, Po was restored to 43% of control values, and only 33% and 38% of controls for ICI- and propranolol-treated rats, respectively. These findings indicate a reduced rate of functional restoration in regenerating muscles with β-antagonist administration, particularly ICI, where Po of injured EDL and soleus muscles was 15% and 23% lower than for injured muscles from saline-treated rats. The impairment in functional recovery with β-AR blockade highlights the role of β-AR signalling in successful muscle repair.

Supported by the National Health & Medical Research Council.