Cholinergic mechanisms in human coronary artery preparations: implications of species differences.

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Abstract
Acetylcholine [ACh] dilates most arteries, including dog coronaries, if the endothelium is intact. Only contraction of human coronary arteries to ACh was shown. Both strip and ring preparations of human coronary epicardial vessels, the latter done particularly to protect the intimal surface from unintentional denudation, contracted to ACh at low to high concentrations (6.84 .times. 10-9-2.05 .times. 10-5 M). Thes responses were blocked by atropine (3.45 .times. 10-6 M). ACh contracted the arteries about as much as ergonovine and considerably more than noradrenaline [norepinephrine]. Field stimulation of coronary artery strips caused a vasoconstriction which was partially antagonized by atropine (3.45 .times. 10-6 M). The release of [3H]NE from superfused coronary artery preparations during field stimulation was inhibited by methacholine (6.24 .times. 10-6 M), a stable muscarinic analogue of ACh. Dog coronary arteries relaxed to ACh but not if the endothelium was intentionally denuded, in which case there was either no response at all or a weak relaxation. Coronary arteries of sheep, pig and cattle always contracted to ACh, and those of monkey contracted in 2 of 3 responsive preparations. Histological examination of the intimal surface of human coronary vascular segments confirmed the presence of an intact endothelial cell layer. Rabbit aorta gave dilator responses to ACh even after being left in the animal for as long after death as the human arteries had been; they did not give dilator responses after the endothelium was rubbed off. Cholinergic vasoconstriction of coronary arteries occurs in humans, though not in the dog and is probably important in some cases of coronary artery spasm.