We examined the effects of angiotensin II (Ang II) and Ang-(l-7) on the release of [

The contractile responses to transmural stimulation of, and the overflow of tritium from the rat portal vein prelabelled with 3H-noradrenaline were studied. The contractile responses of the rat portal vein were sustained throughout the period of stimulation. The tension developed did not decline when two consecutive periods of stimulation were compared. In contrast, the tritium overflow decreased during the second period of stimulation. Preincubation with 3 micronM phenoxybenzamine during 30 min increased 3-fold the tritium overflow during stimulation. Phentolamine and phenoxybenzamine were nearly equipotent in reducing the vascular response to stimulation. In contrast, phentolamine was less potent than phenoxybenzamine in increasing the 3H-noradrenaline overflow elicited by stimulation. The results obtained with phentolamine are interpreted in terms of a different potency of phentolamine to produce blockade of prejunctional and postjunctional alpha-adrenoceptors in the rat portal vein. ATP inhibited by 70% the tritium overflow induced by stimulation. The potency of ATP in inhibiting the overflow increased when the prejunction alpha-adrenoceptors were blocked. The purine compounds ATP, ADP, AMP and adenosine were roughly equipotent in inhibiting stimulation-induced tritium overflow. The tritium released by stimulation decreased when uptake and metabolism of adenosine were inhibited. Under physiological conditions, a prejunctional purinergic inhibition of noradrenaline release might be involved in an endogenously mediated negative feed-back regulatory mechanism. It is possible that the purinergic inhibition of the noradrenaline liberation elicited by stimulation plays a physiological role in tissues with both purinergic and adrenergic innervation.

Summary1. The effects of depletion of endogenous noradrenaline by reserpine-pretreatment on [3H]-noradrenaline overflow elicited by nerve stimulation were determined in the isolated nerve-muscle preparation of the cat's nictitating membrane.2. Reserpine pretreatment (0 3 mg/kg, s.c., 4 days prior to the experiment) reduced the noradrenaline levels in the smooth muscle of the nictitating membrane to about 10% of the control values while granular retention of [3H]-noradrenaline had recovered to nearly 40% of the controls. 3. In the reserpine-pretreated tissue the fraction release per shock induced by nerve stimulation was 2-2-fold higher than the value obtained in the untreated tissues. This effect was correlated with the degree of depletion of the noradrenaline stores rather than with the decrease in the response of the effector organ.4. Phenoxybenzamine, 2-9 /.M reduced the responses to nerve stimulation to the same extent in control and in reserpine-pretreated tissues. Yet, this concentration of phenoxybenzamine increased by 13-fold the overflow of the labelled transmitter in the controls and only by 3-fold in reserpine-pretreated tissues. 5. The decrease in effectiveness of phenoxybenzamine in enhancing transmitter overflow after reserpine-pretreatment appears to be due to the decrease in the total release of the transmitter. 6. The results obtained support the view that in reserpine-pretreated tissues decreased transmitter output reduces the activation of the presynaptic a-adrenoceptors which mediate the negative feed-back mechanism that regulates transmitter release by nerve stimulation.