APPS November 2002 Meeting Abstract 1120


FENOTEROL TREATMENT REVERSES SARCOPENIA AND IMPROVES MUSCLE FUNCTION IN AGED RATS

James G. Ryall, David R. Plant, Paul Gregorevic, Gordon S. Lynch, Muscle Mechanics Laboratory, Department of Physiology, The University of Melbourne, Victoria, 3010, Australia.

Ageing is associated with progressive muscle wasting and weakness and in the very frail and elderly, the loss of muscle mass can be so severe it can impact upon the ability to perform the tasks of everyday living. In high doses, β2-agonists (such as the most widely described, clenbuterol) have potent muscle anabolic effects and have therefore been proposed as possible therapeutic agents to combat age-related muscle wasting.1 We have demonstrated that another β2-agonist, fenoterol, has more potent anabolic effects on skeletal muscle than clenbuterol.2 We tested the hypothesis that fenoterol treatment could reverse the muscle atrophy and weakness in skeletal muscles of very old Fischer 344 rats. Adult (16 months/age) and old (28 months/age) rats were treated daily with either fenoterol (1.4 mg/kg/day, i.p ~0.5 mL total volume) or saline vehicle for four weeks. Following treatment, rats were anaesthetized with sodium pentobarbitone and the fast-twitch extensor digitorum longus (EDL) and predominantly slow-twitch soleus muscles were surgically excised from the hindlimb for determination of isometric contractile properties in vitro. Muscle mass was lower in old compared with adult rats indicative of sarcopenia (EDL: adult 163 5 mg (n = 10) vs old: 145 5 mg (n = 9); soleus: adult 148 3 mg (n = 10) vs old: 130 3 mg (n = 9)). Maximum force was lower in both EDL and soleus muscles of old compared with adult rats (EDL: adult 3324 65 mN vs old: 2911 84 mN; soleus: adult 1811 57 mN vs old: 1597 33 mN, P < 0.05). In old rats fenoterol treatment increased EDL and soleus muscle mass and force to levels equivalent to untreated adult rats. We conclude that fenoterol is a powerful anabolic agent that can reverse muscle wasting and weakness in old rats and has therapeutic potential for sarcopenia.

(1) Lynch GS. Expert Opinion on Therapeutic Patents. 2002;12:11-27.

(2) Ryall JG, Gregorevic P, Plant DR, Sillence MN, Lynch GS. American Journal of Physiology. 2002. in review.

Supported by the Muscular Dystrophy Association (USA).


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