Effects of alpha 1- and alpha 2-adrenoceptor blocking drugs on noradrenaline release rate in anesthetized rabbits

[3H]noradrenaline was infused intravenously into pentobarbitone-anesthetized rabbits to reach a steady-state plasma (3H]noradrenaline level, from which the noradrenaline plasma clearance was calculated. The plasma level of endogenous noradrenaline was determined simultaneously, and the rate of noradrenaline release was then derived. The effects of a series of selective alpha 1- and alpha 2-adrenoceptor blocking drugs on the noradrenaline release rate and noradrenaline clearance were investigated. Yohimbine (1 mg/kg i.v.), rauwolscine (1 mg/kg i.v.), corynanthine (1 mg/kg i.v.), prazosin (0.3 and 1 mg/kg i.v.), phenoxybenzamine (4 mg/kg i.v.), and sodium nitroprusside (10 micrograms/kg/min i.v.) decreased the plasma noradrenaline clearance. The selective alpha 2-adrenoceptor blocking drugs yohimbine and rauwolscine, as well as phenoxybenzamine, increased the noradrenaline release rate more than equihypotensive doses of the directly acting vasodilators hydralazine and sodium nitroprusside. The selective alpha 1-adrenoceptor blocking drugs prazosin and corynanthine increased the noradrenaline release rate less than equihypotensive doses of the vasodilators. These results suggest that, in vivo, blockade of alpha 2-adrenoceptors results in increased noradrenaline release, probably due to blockade of inhibitory presynaptic alpha 2-adrenoceptors at sympathetic nerve endings. Blockade of alpha 1-adrenoceptors, on the other hand, appears to depress baroreceptor-mediated increases in noradrenaline release in response to a fall in blood pressure.