Research Institute for Sports and Exercise Sciences, Liverpool John Moores University, Liverpool, United Kingdom.
High doses of the beta2-adrenergic receptor (AR) agonist, Clenbuterol, can induce necrotic myocyte death in the heart and slow-twitch skeletal muscle of the rat. However, it is not known if this agent can also induce myocyte apoptosis and whether this would occur at a lower dose than previously reported for myocyte necrosis. Male Wistar rats were given single subcutaneous injections of Clenbuterol. Immunohistochemistry was used to detect myocyte specific apoptosis (detected on cryosections using a caspase 3 antibody and confirmed using annexin V, single-strand DNA labelling and TUNEL). Myocyte apoptosis was first detected at 2 h, and peaked 4 h after Clenbuterol administration. The lowest dose of Clenbuterol to induce cardiomyocyte apoptosis was 1 microg kg(-1), with peak apoptosis (0.35 +/- 0.005 %; P<0.05) occurring in response to 5 mg kg(-1) . In the soleus, peak apoptosis (5.8 +/- 2 %; P<0.05) was induced by the lower dose of 10 microg kg(-1). Cardiomyocyte apoptosis occurred throughout the ventricles, atria and papillary muscles. However, this damage was most abundant in the left ventricular subendocardium at a point 1.6 mm, that is, approximately one-quarter of the way from the apex towards the base. beta-AR antagonism (involving propranolol, bisoprolol or ICI 118,551) or reserpine was used to show that Clenbuterol-induced myocardial apoptosis was mediated through neuromodulation of the sympathetic system and the cardiomyocyte beta1-AR, whereas in the soleus direct stimulation of the myocyte beta2-AR was involved. These data show that when administered in vivo, beta2-AR stimulation by Clenbuterol is detrimental to cardiac and skeletal muscles even at low doses, by inducing apoptosis through beta1- and beta2-AR, respectively.
All very interesting but Clenbuterol has also been proven to be Anabolic in horses so what gives