A pharmacodynamic study on clenbuterol-induced toxicity: β1- and β2-adrenoceptors involvement in guinea-pig tachycardia in an in vitro model

β2-Receptor adrenergic agonists as clenbuterol and analogues are illegally used as growth promoters in cattle, in Europe, as well as in other countries. Following consumption of meat or liver, intoxication cases were described, and cardiovascular toxic effects (tachycardia, hypertension) were of clinical relevance. Therefore, we investigated whether heart rate increase induced by clenbuterol could depend upon stimulation of β1- and/or β2-adrenergic receptors, and in which ratio. We used in vitro guinea-pig atria, a model in which β1-/β2-receptors ratio is similar to that found in men. In our experiments both β1- and β2-receptors contributed to clenbuterol-induced heart rate increase, but with a different potency. The selective β2-antagonist ICI-118,551 competitively antagonized responses to clenbuterol with high affinity (pA2 9.47 ± 0.28, SchildSlope 0.98 ± 0.20 not significantly different from unity, KB 0.34 nM). The selective β1-antagonist atenolol antagonized clenbuterol with a relatively lower affinity (pA2 = 7.59 ± 0.14), the SchildSlope = 1.97 ± 0.33 was significantly different from unity (P < 0.05). Results show that clenbuterol stimulates guinea-pig heart rate by acting chiefly on β2-adrenoceptor, although responses to clenbuterol apparently are mediated by an inter-play between both β-adrenoceptors. Further experiments are necessary to understand which β-adrenergic antagonists are of effectiveness to counteract cardiovascular effects in case of intoxication following clenbuterol, or other β-adrenergic stimulants.