EFFECT OF CLENBUTEROL ON THE MODULATION OF NORADRENALINE RELEASE IN THE RAT TAIL ARTERY

1 Exposure of rat tail arteries to clenbuterol, a beta(2)-adrenoceptor agonist, for 20 or 90 min, did not change or increase, respectively, tritium overflow induced by electrical field stimulation in arteries p reincubated with [H-3]-noradrenaline (NA). This facilitatory effect wa s antagonized by propranolol. 2 Phentolamine increased the evoked over flow four-fold, which was not modified by 90 min incubation with clenb uterol. In rats pretreated with clenbuterol for 2 weeks, the stimulate d overflow was not enhanced by this beta(2)-agonist, and the increase produced by phentolamine was markedly diminished. 3 Contractile respon ses induced by electrical field stimulation were not modified or incre ased (only at low frequencies) by preincubation with clenbuterol for 2 0 or 90 min, respectively. This effect was inhibited by propranolol. 4 In arteries precontracted with 5-hydroxytryptamine, clenbuterol (10 n M - 10 mu M) produced small relaxations, which were reduced by propran olol plus phentolamine and not modified by phentolamine or 90 min expo sure to clenbuterol. 5 These results indicate that prolonged exposure of rat tail arteries to clenbuterol produces a facilitation of NA rele ase mediated by activation of presynaptic beta(2)-adrenoceptors, which may be involved on the enhancement of contractile responses to electr ical stimulation induced by clenbuterol. However, chronic treatment wi th this beta-agonist desensitizes these receptors.