BACKGROUND: Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. METHODS AND RESULTS: Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N(G)-monomethyl-L-arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting 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 x mL(-1) x 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 CVR 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 x mL(-1) x 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% versus 0.0+/-2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-mediated 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 the 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.
BACKGROUND: Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. METHODS AND RESULTS: Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N(G)-monomethyl-L-arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting 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 x mL(-1) x 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 CVR 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 x mL(-1) x 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% versus 0.0+/-2.9%, P = 0.02) abolished pacing-induced conduit vessel flow-mediated 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 the 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.
Authors: Aaron H Bubolz; Suelhem A Mendoza; Xiaodong Zheng; Natalya S Zinkevich; Rongshan Li; David D Gutterman; David X Zhang Journal: Am J Physiol Heart Circ Physiol Date: 2011-12-02 Impact factor: 4.733
Authors: Zhichao Zhou; Uthra Rajamani; Hicham Labazi; Stephen L Tilley; Catherine Ledent; Bunyen Teng; S Jamal Mustafa Journal: Purinergic Signal Date: 2015-04-25 Impact factor: 3.765