THE ACETYLCHOLINE PARADOX - A CONSTRICTOR OF HUMAN SMALL CORONARY-ARTERIES EVEN IN THE PRESENCE OF ENDOTHELIUM

1. In animal experiments, acetycholine is generally a vasodilator acting indirectly by releasing endothelium-derived relaxing factor (EDRF); for example, in dog and rabbit small coronaries mounted in a myograph, acetylcholine caused concentration-dependent relaxation. 2. In human small coronary arteries taken from the atrial appendage, however, acetycholine caused concentration-dependent contraction with a funcionally intact endothelium as shown by the relaxation in response to substance P, another stimulant of EDRF release. 3. We propose that coronary microvessels from various species have variable populations of acetylcholine receptors on the medial smooth muscle that cause contraction and on the endothelium that cause the release of EDRF. In humans, the medial smooth muscle receptors appear to predominate, and may thus play a role in coronary vasoconstriction.