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Keywords:

  • Adrenergic;
  • heart;
  • cardiac hypertrophy;
  • receptors
  • β2-Adrenoceptor agonists provide a potential therapy for muscle wasting and weakness, but their use may be limited by adverse effects on the heart, mediated in part, by β1-adrenoceptor activation.

  • Two β2-agonists, formoterol and salmeterol, are approved for treating asthma and have an extended duration of action and increased safety, associated with greater β2-adrenoceptor selectivity.

  • The pharmacological profiles of formoterol and salmeterol and their effects on skeletal and cardiac muscle mass were investigated in 12-week-old, male F344 rats. Formoterol and salmeterol were each administered via daily i.p. injection at one of seven doses (ranging from 1 to 2000 μg kg−1 day−1), for 4 weeks. Rats were anaesthetised and the EDL and soleus muscles and the heart were excised and weighed. Dose–response curves were constructed based on skeletal and cardiac muscle hypertrophy.

  • Formoterol was more potent than salmeterol, with a significantly lower ED50 in EDL muscles (1 and 130 μg kg−1 day−1, P <0.05), whereas salmeterol had greater intrinsic activity than formoterol in both EDL and soleus muscles (12% greater hypertrophy than formoterol). The drugs had similar potency and intrinsic activity in the heart, with a smaller leftward shift for formoterol than seen in skeletal muscle. A dose of 25 μg kg−1 day−1 of formoterol elicited greater EDL and soleus hypertrophy than salmeterol, but resulted in similar β-adrenoceptor downregulation.

  • These results show that doses as low as 1 μg kg−1 day−1 of formoterol can elicit significant muscle hypertrophy with minimal cardiac hypertrophy and provide important information regarding the potential therapeutic use of formoterol and salmeterol for muscle wasting.

British Journal of Pharmacology (2006) 147, 587–595. doi:10.1038/sj.bjp.0706669