Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans

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Abstract

Background. NG-Monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthesis, was used to determine the effects of inhibition of nitric oxide synthesis in the human coronary circulation. Methods and Results. Twelve patients (mean age, 52±2 years) with normal epicardial coronary arteries were studied. The surface ECG, systemic blood pressure, and coronary venous oxygen saturation (coronary SvO2), an index of coronary blood flow, were monitored continuously. Coronary artery diameter was measured by quantitative arteriography. L-NMMA was given as intracoronary infusions at 2 mL/min via the diagnostic arteriography catheter. In two patients, low doses (0.01 to 5 μmol/min) of L-NMMA were infused into the nondominant right coronary artery. There was no evidence of ischemia in these patients, who were not included in the final analysis. In 10 patients, higher doses of L-NMMA (4, 10, and 25 μmol/min, each for 5 minutes) were infused into the left coronary artery. In six patients, incremental doses of acetylcholine were infused (1, 10, and 100 nmol/min, each for 3 minutes) before and after the L-NMMA infusion. Finally, in all patients, sodium nitroprusside, a nitric oxide donor, was infused. No patient developed myocardial ischemia. The heart rate and systemic blood pressure remained unchanged throughout the infusions. L-NMMA (25 μmol/min), compared with the control saline infusion, caused a significant reduction in distal (-5.9±2.1%, P=0.021) but not proximal left anterior descending coronary artery (LAD) diameter and a fall in coronary SvO2 from 37.5±2.8% to 34.3±2.8% (P=0.019). Sodium nitroprusside dilated the proximal (17.8±6.9%, P=0.033) and distal (24.5±6.5%, P=0.006) LAD and increased the coronary SvO2 to 61.6±5.0% (P=0.0002). Acetylcholine caused significant dilatation of the distal (13.8±5.4%, P=0.049) but not proximal LAD and a significant increase in coronary SvO2 from 36.5±3.5% to 59.2±2.8% (P<0.0001). After L-NMMA, acetylcholine-induced dilatation of the distal LAD was abolished, but the rise in coronary SvO2 was unchanged. Conclusions. Inhibition of nitric oxide synthesis in the human coronary circulation caused a decrease in basal distal LAD diameter and basal coronary blood flow assessed by coronary SvO2, indicating that there is a small basal release of nitric oxide in the distal epicardial coronary arteries and resistive vessels. Distal epicardial coronary artery dilatation in response to acetylcholine is nitric oxide dependent, but coronary resistive vessel dilatation is not.

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APA

Lefroy, D. C., Crake, T., Uren, N. G., Davies, G. J., & Maseri, A. (1993). Effect of inhibition of nitric oxide synthesis on epicardial coronary artery caliber and coronary blood flow in humans. Circulation, 88(1), 43–54. https://doi.org/10.1161/01.CIR.88.1.43

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