The chronic effects of beta-adrenoreceptor blocking agents on transmitter overflow in the anococcygeus muscle of the rat.

1 The effect of chronic administration of three beta-adrenoreceptor blocking agents, propranolol, timolol and atenolol on transmitter release from sympathetic nerves has been investigated in the isolated anococcygeus muscle of the rat. 2 Oral treatment for 11 weeks with either propranolol (12 mg/kg/day), or timolol (1.2 mg/kg/day) but not atenolol (12 mg/kg/day) significantly increased the stimulation-induced overflow of radioactivity following preincubation of the tissue with 3H-NA. 3 No increase in end-organ sensitivity, as measured in terms of responsiveness to exogenous acetylcholine, tyramine or NA, was observed. 4 The ineffectiveness of atenolol compared to the other beta-adrenoreceptor blocking drugs may be related to the finding that, in acute experiments, atenolol inhibited tissue uptake of 3H-NA. 5 It is postulated that increased release of transmitter may be related to prolonged blockade of presynaptic beta-receptors and a resultant increase in presynaptic receptor sensitivity.