Flow-mediated vasodilation of human epicardial coronary arteries: effect of inhibition of nitric oxide synthesis

Objectives. This study sought to investigate the role of nitric oxide, an endothelium-derived relaxing factor, in flow-mediated vasodilation in human epicardial coronary arteries. Background. Endothelium-derived relaxing factors may be released from the coronary artery endothelium in response to increases in blood flow. Methods. We studied the effect of the nitric oxide synthesis inhibitor NG-monomethyl-l-arginine (l-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler flow velocity measurements. Adenosine at 100 μg/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood flow. Acetylcholine at 3 and 30 μg/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetykholine were infused before and after the intracoronary infusion ofl-NMMA (25 μg/min for 5 min). Results. Infusion ofl-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 ± 0.14 to 2.74 ± 0.13 mm [mean ± SEM], p < 0.01). Adenosine increased coronary blood flow Wore and afterl-NMMA (+3995 ± 27.5% and +511.9 ± 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and afterl-NMMA (+9.2 ± 1.5%, p < 0.01 and +8.6 ± 2.1%, p < 0.01, respectively). A dose of 3 μg/min of acetylcholine significantly dilated the proximal left anterior descending artery beforel-NMMA (+7.6 ± 1.0%, p < 0.01), but acetylcholine-induced vasodilation was attenuated afterl-NMMA (−1.8 ± 1.0%). Conclusions. Our data suggest that nitric oxide modulates basal coronary artery tone but that mediators other than nitric oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries.