A muscarinic inhibition of the noradrenaline release evoked by postganglionic sympathetic nerve stimulation

Summary

• 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.