Contribution of vasodilator prostanoids and nitric oxide to resting flow, metabolic vasodilation, and flow-mediated dilation in human coronary circulation

Background-Endothelial dysfunction is associated with atherosclerosis and m ay contribute to ischemic syndromes. We assessed the contribution of endoth elium-derived nitric oxide (NO) and vasodilator prostanoids to resting bloo d flow, metabolic vasodilation, and flow reserve in the human coronary circ ulation. Methods and Results-Coronary hemodynamics were assessed before and after in hibition of vasodilator prostanoids and NO with intracoronary aspirin (acet ylsalicylic acid [ASA]) and N-G-monomethyl-L-arginine (L-NMMA), respectivel y. Angiographically smooth or mildly irregular vessels, with normal adenosi ne-induced coronary flow reserve, were studied in 25 patients undergoing cl inically indicated procedures. Coronary blood velocity was measured by Dopp ler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced re sting conduit vessel diameter by 11% (P = 0.003) and CBF by 27% (P = 0.008) and increased coronary vascular resistance (CVR) by 24% (P < 0.0001). ASA attenuated pacing-induced hyperemia by 28% (45.0 +/- 4.6 versus 32.6 +/- 3. 4 mL/min, P = 0.005) and increased minimum CVR by 39% (2.8 +/- 0.3 versus 3 .9 +/- 0.5 mm Hg.mL(-1).min(-1), P = 0.007). L-NMMA reduced resting conduit vessel diameter by 9% (P = 0.05) and CBF by 20% (P = 0.08) and increased C VR by 19% (P = 0.03). L-NMMA attenuated pacing-induced hyperemia by 20% (42 .4 +/- 5.1 versus 34.1 +/- 3.4 mL/min, P = 0.04) and increased minimum CVR by 33% (2.9 +/- 0.4 versus 3.8 +/- 0.5 mm Hg.mL(-1).min(-1), P = 0.02). ASA (7.7 +/- 2.3% versus -1.6 +/- 3.2%, P = 0.06) and L-NMMA (12.1 +/- 3.9% ve rsus 0.0 +/- 2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-m ediated dilation. Conclusions-Tonic release of vasodilator prostanoids and NO contributes to resting conduit and resistance vessel tone and to peak functional hyperemia and flow-mediated dilation after metabolic stimulation. This underscores t he importance of normal endothelial function for metabolic vasodilation and suggests that it may be a key mechanism for preventing myocardial ischemia in coronary artery disease.