Nifedipine does not impede clenbuterol-stimulated muscle hypertrophy.
The mechanism(s) responsible for beta2-adrenergic receptor-mediated skeletal muscle and cardiac hypertrophy remains undefined. This study examined whether calcium influx through L-type calcium channels contributed to the development of cardiac and skeletal muscle (plantaris; gastrocnemius; soleus) hypertrophy during an 8-day treatment with the beta2-adrenergic receptor agonist clenbuterol. Concurrent blockade of L-type calcium channels with nifedipine did not reverse the hypertrophic action of clenbuterol. Moreover, nifedipine treatment alone resulted in both cardiac and soleus muscle hypertrophy (6% and 7%, respectively), and this effect was additive to the clenbuterol-mediated hypertrophy in the heart and soleus muscles. The hypertrophic effects of nifedipine were not associated with increases in total beta-adrenergic receptor density, nor did nifedipine reverse clenbuterol-mediated beta-adrenergic receptor downregulation in either the left ventricle or soleus muscle. Both nifedipine and clenbuterol-induced hypertrophy increased total protein content of the soleus and left ventricle, with no change in protein concentration. In conclusion, our results support the hypothesis that beta2-adrenergic receptor agonist-induced muscle hypertrophy is mediated by mechanisms other than calcium influx through L-type calcium channels.
Murphy
R J
RJ
Département de Kinésiologie, Université de Montréal, Montreal, Canada H3C 3J7.
Béliveau
L
L
Gardiner
P F
PF
Calderone
A
A
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D020746:Calcium Channels, L-Type; D006332:Cardiomegaly / Q000139:chemically induced; D002976:Clenbuterol / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000187:drug effects*; D006984:Hypertrophy / Q000139:chemically induced; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009124:Muscle Proteins; D009543:Nifedipine; D002118:Calcium; D002976:Clenbuterol