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 relating factors may be re leased from the coronary artery endothelium in response to increases in blood flow. Methods. We studied the effect of the nitric oxide synthesis inhibitor N-G-monomethyl-L-arginine (L-NMMA) on the flow-mediated vasodilation of epicardial coronary arteries in 12 patients, using quantitative angiographic and Doppler bow velocity measurements, Adenosine at 100 mu g/min was infused into the left anterior descending coronary artery to test the dilator response of the proximal artery to increases in blood bow. Acetylcholine at 3 and 30 mu g/min was infused into the left coronary ostium to determine endothelium-dependent vasodilation of the proximal left anterior descending artery. Adenosine and acetylcholine were infused before and after the intracoronary infusion of L-NMMA (25 mu mol/min for 5 min). Results. Infusion of L-NMMA caused a significant decrease in the baseline diameter of the proximal left anterior descending artery (from 2.90 +/- 0.11 to 2.74 +/- 0.13 mm [mean a SEM], p < 0.01), Adenosine increased coronary blood how before and after L-NMMA (+399.5 +/- 27.5% and +511.9 +/- 33.3%, respectively). Flow-mediated vasodilation was observed in the proximal left anterior descending artery before and after L-NMMA (+9.2 +/- 1.5%, p < 0.01 and +8.6 +/- 2.1%, p < 0.01, respectively). A dose of 3 mu g/min of acetylcholine significantly dilated the proximal left anterior descending artery before L-NMMA (+7.6 +/- 1.0%, p < 0.01), but acetylcholine induced vasodilation was attenuated after L-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.