title: Evidence of endothelial dysfunction in angiographically normal coronary arteries of patients with coronary artery disease.
abstract: Acetylcholine causes endothelium-dependent dilation of normal arteries in most animal species. The effect of acetylcholine on normal human coronary arteries is controversial. Pathologic studies and epicardial echocardiography have shown that diffuse atherosclerosis is often present despite angiographic evidence of discrete coronary artery disease (CAD). Therefore, we postulated that acetylcholine would cause vasoconstriction of coronary arteries that are angiographically normal in patients with CAD. Coronary artery diameter, measured by automated quantification of digitized cineangiograms, was determined before and after the intracoronary infusion of 0.2 mM acetylcholine at 0.8-1.6 ml/min. The diameter of stenotic or irregular segments of six atherosclerotic coronary arteries decreased from 1.80 +/- 0.42 mm before acetylcholine to 1.26 +/- 0.46 mm after acetylcholine (p = 0.0025). Acetylcholine had a significantly different effect on the diameter of two groups of coronary arteries that are angiographically normal. Acetylcholine caused a 0.16 +/- 0.09-mm increase in the diameter of 14 normal coronary arteries in patients without CAD, whereas it caused a 0.26 +/- 0.12-mm decrease in the diameter of 14 normal coronary arteries in patients with CAD (p less than 0.01). Thus, the normal response to intracoronary acetylcholine is vasodilation, suggesting that endothelium-derived relaxing factor is released from normal human coronary endothelium. The vasoconstrictive effect of acetylcholine in the angiographically normal coronary arteries of patients with CAD suggests the presence of a diffuse abnormality of endothelial function.
authors.affiliation: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor.
authors.forename: S W
authors.initials: SW
authors.lastname: Werns
authors.forename: J A
authors.initials: JA
authors.lastname: Walton
authors.forename: H H
authors.initials: HH
authors.lastname: Hsia
authors.forename: E G
authors.initials: EG
authors.lastname: Nabel
authors.forename: M L
authors.initials: ML
authors.lastname: Sanz
authors.forename: B
authors.initials: B
authors.lastname: Pitt
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000792:Angiography; D017023:Coronary Angiography; D003327:Coronary Disease / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003331:Coronary Vessels / Q000187:drug effects / Q000503:physiopathology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D014661:Vasoconstriction
chemical_list: D000109:Acetylcholine