Dual effect of adrenaline on noradrenaline release in the pithed rabbit

We examined the effects of adrenaline on the noradrenaline release rate and plasma catecholamine levels in the pithed rabbit with electrically stimulated sympathetic outflow (3 Hz). Adrenaline (0.06 micrograms/kg/min) increased the rate of noradrenaline release into the plasma. This increase was prevented by propranolol (0.2 mg/kg + 0.1 mg/kg/h) and probably involves activation of presynaptic beta-adrenoceptors. A higher dose of adrenaline (1.0 micrograms/kg/min) significantly reduced the noradrenaline release rate. The reduction was "reversed" to a facilitatory effect by phenoxybenzamine (4 mg/kg). Propranolol alone slightly inhibited the noradrenaline release rate. After pretreatment with desipramine (1.0 mg/kg + 0.2 mg/kg/h), the inhibitory effect of propranolol on noradrenaline release was more pronounced and blood pressure was also lowered. However, in rabbits pretreated with captopril (1 mg/kg) in addition to desipramine, the sympathoinhibitory effect of propranolol was not observed. These results suggest that adrenaline can activate either presynaptic beta-adrenoceptors to increase noradrenaline release or, in higher doses, presynaptic alpha-adrenoceptors to inhibit noradrenaline release in vivo. The decrease in the noradrenaline release rate produced by propranolol alone may not be due to blockade of facilitatory presynaptic beta-adrenoceptors, but rather to depression of renin secretion. This would decrease angiotensin II formation and hence decrease the presynaptic release-enhancing effect of angiotensin II.