Dual effects of clonidine on rat prejunctional alpha-adrenoceptors

1. The effects of clonidine (1.0 mumol/l) and phentolamine (3.0 mumol/l) on the stimulation-induced efflux of radioactivity were assessed in rat isolated atria and tail arteries in which transmitter stores had been labelled with (3H)-noradrenaline. 2. In atria, clonidine did not affect transmitter release when stimulation was for 10 s periods at frequencies of 1, 2 or 5 Hz, whereas at 10 Hz there was a significant 1.2-fold enhancement of release. Phentolamine enhanced release with stimulation at 5 Hz and 10 Hz by 1.5- and 2.5-fold respectively. 3. In tail arteries, clonidine reduced release when stimulation was for 30 s periods at a frequency of 1 Hz, but did not affect release at 2 Hz or 5 Hz. Phentolamine in each case produced an approximately 1.5-fold enhancement of release. 4. In the pithed rat, spinal stimulation of cardioaccelerator fibres produced a tachycardia, the magnitude of which depended on the frequency and duration of stimulation. Clonidine (10 micrograms/kg, i.v.) caused either a reduction or an enhancement of the response depending on the frequency and duration of stimulation; in the presence of phentolamine (2 mg/kg, i.v.), clonidine had no effect. 5. The results are consistent with partial agonistic actions of clonidine at prejunctional alpha-adrenoceptors in the rat cardiovascular system; such effects may be of relevance to the mechanism of the clonidine withdrawal syndrome.