Cholinergic inhibition of adrenergic transmission

Abstract

Acetylcholine has a dual direct effect on vascular smooth muscle. Low concentrations cause relaxation and high concentrations contraction of arteries; veins only contract when exposed to acetylcholine. Both the inhibitory and excitatory component are inhibited by atropine, suggesting the presence of two muscarinic receptors in vascular smooth muscle; depending on their relative distribution, relaxation, biphasic responses, or contractions are obtained. Since only arteries and arterioles are innervated by cholinergic nerves, and since only high concentrations of acetylcholine constrict arteries it is likely that in the intact organism only the relaxatory effect of acetylcholine is of importance. During sympathetic nerve stimulation, acetylcholine in concentrations causing relaxation of arterial smooth muscle reversibly inhibits adrenergic neurotransmission, by decreasing the amount of norepinephrine released by the nerve impulses. This effect can be demonstrated throughout the vascular tree, and in the intact animal. It is due to activation of muscarinic receptors resulting in hyperpolarization of the adrenergic nerve terminals. The inhibition of adrenergic neurotransmission concurs with the direct relaxatory effect of acetylcholine on arterial smooth muscle, and explains part of the potent dilator effects of the drug in the intact organism. Particularly in the case of neurogenic cholinergic vasodilatation, this mechanism must allow a very effective control, since on release of the inhibitory agonist the liberation of the excitatory transmitter is automatically interrupted.