A MUSCARINIC INHIBITION OF NORADRENALINE RELEASE EVOKED BY POSTGANGLIONIC SYMPATHETIC NERVE STIMULATION

1. The noradrenaline output from isolated rabbit hearts perfused with Tyrode solution was estimated fluorimetrically. The postganglionic sympathetic nerves of the heart were stimulated (10 shocks/sec; 1 msec) for three 1 min periods with intervals of 10 min. 2. The noradrenaline output evoked by 3 consecutive stimulation periods decreased exponentially. 3. Acetylcholine (10-9-10-6 g/ml) administered continuously one min before to one min after the second stimulation caused a dose-dependent reduction of the noradrenaline output evoked by the second stimulation to as low as 19% of the normal value. Acetylcholine in the concentrations applied did not cause a noradrenaline output by itself. 4. The inhibitory action of acetylcholine 10-6 g/ml was fully antagonized by atropine 10-6 g/ml, whereas hexamethonium 3×10-6 g/ml had no significant antagonistic effect. 5. The noradrenaline output caused by nerve stimulation was not decreased in the presence of DMPP 10-6 g/ml. DMPP 10-5 g/ml applied 3 min before electrical nerve stimulation caused an output of noradrenaline for 2 min but did not inhibit the noradrenaline release by nerve stimulation. 6. Tyramine 5×10-6 g/ml was administered to the rabbit heart for two 6 min periods at an interval of 15 min. Methacholine 7.4×10-5 g/ml or atropine 1-6 g/ml if present during the second tyramine infusion did not alter the noradrenaline output produced by tyramine. 7. It is concluded that low concentrations of acetylcholine by stimulating muscarinic inhibitory receptors interfere with the noradrenaline release from the postganglionic sympathetic nerve fibres evoked by electrical nerve stimulation. The possibility of a peripheral direct interaction of the cholinergic with the adrenergic nervous system is discussed. © 1969 Springer-Verlag.