Constrictor and dilator responses to intracoronary acetylcholine in adjacent segments of the same coronary artery in patients with coronary artery disease. Endothelial function revisited.

BACKGROUNDIn patients with angiographically detectable atherosclerosis or in those with risk factors for coronary artery disease, intracoronary acetylcholine causes coronary constriction instead of endothelium-derived relaxing factor-mediated dilation. Therefore, it has been hypothesized that diffuse endothelial dysfunction precedes development of coronary atherosclerosis. We tested this hypothesis in a systematic investigation of the effects of ascending doses of acetylcholine on the diameters of nonstenotic segments of the left coronary artery in patients with advanced atherosclerosis and coronary risk factors.METHODS AND RESULTSEffects of intracoronary infusion of acetylcholine (10(-6) to 10(-4) mol/L) on diameters of proximal, middle, and distal nonstenotic segments of the left coronary artery were studied in 28 consecutive patients with chronic stable angina, positive exercise tests, and angiographic evidence of obstructive atherosclerosis (> or = 50% reduction in lumen diameter in at least one vesse...