Acetylcholine has two opposing effects: an endothelium-dependent vasodilator effect and a direct vasoconstrictor effect. The net coronary vasomotor response, either vasodilatation or vasoconstriction, depends on the balance between these two effects. In normal coronary arteries with a functionally intact endothelium, a low concentration of acetylcholine will induce vasodilatation. However, in diseased coronary arteries with dysfunctional endothelium, acetylcholine is expected to induce vasoconstriction even at the same concentration. Thus, a low concentration of acetylcholine, which corresponds to an estimated blood concentration in the coronary bed of 10−8 to 10−6 mol/L, has been used as a probe for testing endothelial function.9 However, even normal coronary arteries with intact endothelial function constrict in response to higher concentrations of acetylcholine by the direct effect of the agent on vascular smooth muscle. The dose of acetylcholine that we used, which corresponds to an estimated blood concentration in the coronary bed of approximately 10−5 mol/L, is so high that the direct vasoconstrictor effect overrides the endothelium-dependent vasodilator effect.,8,10 Thus, a relatively high dose of acetylcholine is not suitable for separating the role of endothelial dysfunction from that of smooth-muscle hyperreactivity in epicardial coronary vasoconstriction.