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-derive d relating factors may be re leased from the coronary artery endotheli um in response to increases in blood flow. Methods. We studied the eff ect of the nitric oxide synthesis inhibitor N-G-monomethyl-L-arginine (L-NMMA) on the flow-mediated vasodilation of epicardial coronary arte ries in 12 patients, using quantitative angiographic and Doppler bow v elocity measurements, Adenosine at 100 mu g/min was infused into the l eft anterior descending coronary artery to test the dilator response o f the proximal artery to increases in blood bow. Acetylcholine at 3 an d 30 mu g/min was infused into the left coronary ostium to determine e ndothelium-dependent vasodilation of the proximal left anterior descen ding artery. Adenosine and acetylcholine were infused before and after the intracoronary infusion of L-NMMA (25 mu mol/min for 5 min). Resul ts. Infusion of L-NMMA caused a significant decrease in the baseline d iameter 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 i n 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 proxim al left anterior descending artery before L-NMMA (+7.6 +/- 1.0%, p < 0 .01), but acetylcholine induced vasodilation was attenuated after L-NM MA (-1.8 +/- 1.0%). Conclusions. Our data suggest that nitric oxide mo dulates basal coronary artery tone but that mediators other than nitri c oxide may be responsible for the flow-mediated vasodilation of human epicardial coronary arteries.