THE CHRONIC EFFECTS OF β-ADRENORECEPTOR BLOCKING AGENTS ON TRANSMITTER OVERFLOW IN THE ANOCOCCYGEUS MUSCLE OF THE RAT

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Abstract
The effect of chronic administration of 3 .beta.-adrenoreceptor blocking agents, propranolol, timolol and atenolol on transmitter release from sympathetic nerves was invesigated in the isolated anococcygeus muscle of the rat. Oral treatment for 11 wk with either propranolol (12 mg/kg per day), or timolol (1.2 mg/kg per day) but not atenolol (12 mg/kg per day) significantly increased the stimulation-induced overflow of radioactivity following preincubation of the tissue with 3H-NA [norepinephrine]. No increase in end-organ sensitivity, as measured in terms of responsiveness to exogenous acetylcholine, tyramine or NA, was observed. 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. Increased release of transmitter may be related to prolonged blockade of presynaptic .beta.-receptors and a resultant increase in presynaptic receptor sensitivity.