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

Acetylcholine dilates most arteries, including dog coronaries, if the endothelium is intact. The present study has shown only contraction of human coronary arteries to acetylcholine. Both strip and ring preparations of human coronary epicardial vessels, the latter done particularly to protect the intimal surface from unintentional denudation, contracted to acetylcholine at low to high concentrations (6.84 X 10(-9)-2.05 X 10(-5) M). These responses were blocked by atropine (3.45 X 10(-6) M). Acetylcholine contracted the arteries about as much as ergonovine and considerably more than noradrenaline. Field stimulation of coronary artery strips caused a vasoconstriction which was partially antagonized by atropine (3.45 X 10(-6) M). The release of [3H]noradrenaline from superfused coronary artery preparations during field stimulation was inhibited by methacholine (6.24 X 10(-6) M), a stable muscarinic analogue of acetylcholine. Dog coronary arteries relaxed to acetylcholine 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 acetylcholine, and those of monkey contracted in two out of three 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 acetylcholine 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. It is concluded that cholinergic vasoconstriction of coronary arteries occurs in humans, though not in the dog, and is probably important in some cases of coronary artery spasm.