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We have investigated the dose- and time-dependency of myocyte apoptosis and necrosis induced by the beta2-adrenergic receptor agonist, clenbuterol, with the aim of determining whether myocyte apoptosis and necrosis are two separate processes or a continuum of events. Clenbuterol has approval for human use as an asthma drug in some countries but is banned for this use in the United States. The present study presents data on clenbuterol-induced necrosis in the heart and soleus muscle of the rat at doses commonly employed to demonstrate its anabolic effects. The dose dependency and time course of cardiac and skeletal myocyte necrosis has been investigated in detail. Clenbuterol is also used as a tocolytic in cattle. The recommended treatment schedule is a single parenteral injection equivalent to 0. Clenbuterol was well absorbed after oral administration to laboratory animals, humans and the target species. In most species peak blood concentrations were achieved 2-3 hours after oral dosing. The incidence of apoptosis in both the heart and soleus muscle reached a maximum 4 h after administration of clenbuterol, whereas the peak incidence of necrosis occurred around 12 h to 15 h. = 4, in each group) received a single injection of 5 mg of clenbuterol kg and were killed at specific time points over a 24-h period. It is conceivable that, like the less selective -ARagonist isoproterenol (3, 27), clenbuterol may inducecell death and necrosis in the heart. Indeed, clen-buterol has previously been shown to induce generalhistological damage in the soleus muscle of the rat inresponse to a dose of 2 mg/kg administered via drink-ing water (36)
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