Paradoxical Vasoconstriction Induced by Acetylcholine in Atherosclerotic Coronary Arteries

Abstract

Acetylcholine is believed to dilate normal blood vessels by promoting the release of a vasorelaxant substance from the endothelium (endothelium-derived relaxing factor). By contrast, if the endothelium is removed experimentally, acetylcholine constricts blood vessels. We tested the hypothesis that muscarinic cholinergic vasodilation is impaired in coronary atherosclerosis. Graded concentrations of acetylcholine and, for comparison, the nonendothelial-dependent vasodilator nitroglycerin were infused into the left anterior descending artery of eight patients with advanced coronary stenoses (greater than 50 percent narrowing), four subjects with angiographically normal coronary arteries, and six patients with mild coronary atherosclerosis (less than 20 percent narrowing). Vascular responses were evaluated by quantitative angiography. In several segments each of four normal coronary arteries, acetylcholine caused a dose-dependent dilation from a control diameter of 1.94 +/- 0.16 mm to 2.16 +/- 0.15 mm with the maximal acetylcholine dose (P less than 0.01). In contrast, all eight of the arteries with advanced stenoses showed dose-dependent constriction, from 1.05 +/- 0.05 to 0.32 +/- 0.16 mm at the highest concentration of acetylcholine (P less than 0.01), with temporary occlusion in five. Five of six vessels with minimal disease also constricted in response to acetylcholine. All vessels dilated in response to nitroglycerin, however. We conclude that paradoxical vasoconstriction induced by acetylcholine occurs early as well as late in the course of coronary atherosclerosis. Our preliminary findings suggest that the abnormal vascular response to acetylcholine may represent a defect in endothelial vasodilator function, and may be important in the pathogenesis of coronary vasospasm.

Arterial stiffness or endothelial dysfunction as a surrogate marker of vascular risk

“…Coronary circulation: Quantitative coronary angiography can be used to examine the change in diameter to intracoronary infusions of the endothelium-dependent vasodilators such as acetylcholine. In healthy vessels, acetylcholine evokes an NO-mediated vasodilatory response; in patients with endothelial dysfunction, this effect is blunted, or paradoxical vasoconstriction may occur (55). Endothelial function of the coronary microvasculature (resistance vessels) can be assessed by employing intracoronary Doppler techniques and assessing coronary blood flow in response to pharmacological or physiological stimuli (56).…”

“…Endothelial injury with resulting dysfunction appears to be the initiating event in atherosclerosis (65)(66)(67) and plays an important role in the ischemic manifestations of coronary disease (55) demonstrated that whereas acetylcholine induces epicardial coronary vasodilation in patients without atherosclerosis, paradoxical vasoconstriction occurs in patients with atherosclerosis. Atherosclerosis also impairs coronary resistance vessel function, despite the fact that resistance vessels are rarely affected by atherosclerosis (56,69).…”

Endothelial dysfunction in cardiovascular disease and Flammer syndrome—similarities and differences

“…In 1986, Ludmer and colleagues [29] demonstrated endothelial dysfunction for the first time in vivo. The authors captured epicardial coronary artery dilatation after acetylcholine intracoronary infusion by quantitative coronary angiography in healthy coronaries with intact endothelium.…”

Asymmetrical dimethylarginine: A novel risk factor for coronary artery disease

“…8 Nitric oxide also contributes importantly to resting vascular tone and acetylcholine-induced vasodilation in normal and atheromatous coronary arteries. 7,[9][10][11][12] However, the mechanism of derangement of L-arginine-NO pathway that leads to endothelial dysfunction is still not fully clear. Recently, asymmetrical dimethylarginine (ADMA) has been implicated as an important contributing factor.…”