The effects of cholinomimetic drugs on responses to sympathetic nerve stimulation and noradrenaline in the rabbit ear artery.

1. The effects of infusions of the cholinomimetic drugs acetylcholine, methacholine, muscarine, carbachol, arecoline and pilocarpine were examined on vasoconstrictor responses of the perfused rabbit ear artery to sympathetic nerve stimulation and to injections of noradrenaline.2. The first effect of very low concentrations of acetylcholine or muscarine was a slight enhancement of responses to sympathetic nerve stimulation, but when higher concentrations of acetylcholine, methacholine, muscarine, carbachol and arecoline were infused, these vasoconstrictor responses were decreased. With still higher concentrations the responses tended to increase in size during the infusion. After stopping an infusion, the depressed vasoconstrictor responses rapidly recovered and became enhanced.3. Infusions of pilocarpine in a wide range of concentrations generally caused enhancement of responses.4. The depressant effects of cholinomimetic drugs on the responses to sympathetic nerve stimulation were antagonized by atropine. Larger concentrations of the drugs overcame the blockade by atropine.5. The effects of acetylcholine, methacholine and muscarine on the responses to sympathetic nerve stimulation were more pronounced at low than at high frequencies of stimulation.6. Vasoconstrictor responses to injected noradrenaline were enhanced by acetylcholine or methacholine, whereas responses to sympathetic nerve stimulation were decreased by the same concentrations of these choline esters.7. It is suggested that cholinomimetic drugs may act on receptor sites associated with the adrenergic terminal axon and that they may facilitate or impair the release of noradrenaline and impair noradrenaline uptake.