Nitric oxide-mediated flow-dependent dilation is impaired in coronary arteries in patients with coronary spastic angina

Division of Cardiology, Kumamoto University School of Medicine, Japan. kiyo@gpo.kumamoto-u.ac.jp

OBJECTIVES: This study sought to examine whether flow-dependent dilation is impaired at the site of coronary artery spasm in patients with coronary spastic angina. BACKGROUND: Physiologic stimuli such as exercise and exposure to cold have been shown to cause an increase in coronary blood flow, leading to flow-dependent dilation of coronary arteries in normal subjects, but cause coronary constriction in patients with coronary spastic angina. METHODS: A maximal increase in blood flow was induced selectively in the left anterior descending coronary artery (LAD) by infusion of adenosine through a Doppler flow catheter tip in the midportion of the LAD in 10 patients with coronary spastic angina, all with angiographically demonstrated spasm of the LAD, and in 11 control patients. Coronary artery diameter at the proximal site of the LAD (exposed to increased flow but not to adenosine) was measured by quantitative angiography. RESULTS: Flow-dependent dilation of the proximal LAD was found to be less in spasm arteries than in control arteries. Infusion of NG-monomethyl-L-arginine (L-NMMA) in the proximal LAD suppressed flow-dependent dilation in control arteries but had no significant effect on spasm arteries. The dilator response to nitroglycerin was not impaired in spasm coronary arteries. CONCLUSIONS: Our results indicate that flow-dependent coronary dilation is impaired in spasm arteries, partly due to a deficiency in endothelial nitric oxide bioactivity, which in turn may contribute to the increase in coronary tone during physiologic stimuli in patients with coronary spastic angina.

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