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

Department of Internal Medicine, Hiroshima University School of Medicine, Japan.

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 micrograms/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 micrograms/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 mumol/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 +/- 0.14 to 2.74 +/- 0.13 mm [mean +/- SEM], p < 0.01). Adenosine increased coronary blood flow 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 micrograms/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.

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