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(Hypertension. 2008;51:127.)
© 2008 American Heart Association, Inc.

Original Articles

The Interaction Between Coronary Endothelial Dysfunction, Local Oxidative Stress, and Endogenous Nitric Oxide in Humans

Shahar Lavi; Eric H. Yang; Abhiram Prasad; Verghese Mathew; Gregory W. Barsness; Charanjit S. Rihal; Lilach O. Lerman; Amir Lerman

From the Division of Cardiovascular Diseases (S.L., E.H.Y., A.P., V.M., G.W.B., C.S.R., L.O.L., A.L.) and Division of Nephrology and Hypertension (L.O.L.), Mayo Clinic, Rochester, Minn.

Correspondence to Amir Lerman, MD, Division of Cardiovascular Diseases, Mayo Clinic, Mary Brigh 4-523, First Street SW, Rochester, MN 55905. E-mail Lerman.Amir{at}mayo.edu

In vitro and animal studies suggest that oxidative stress is associated with endothelial dysfunction. We tested whether local oxidative stress and nitric oxide (NO) bioavailability in the coronary circulation is associated with coronary endothelial dysfunction in humans. Blood samples were obtained simultaneously from the left main coronary artery and the coronary sinus for measurement of F2-isoprostanes, myeloperoxidase, nitrotyrosine, and superoxide dismutase in 20 patients without significant coronary disease. Afterward, coronary blood flow and the vascular response to intracoronary acetylcholine and N^G-monomethyl-_L-arginine (L-NMMA) were assessed. The gradient of isoprostanes between the arterial levels and coronary sinus correlated with the change in coronary artery diameter in response to acetylcholine (r=–0.79, P<0.0001). Isoprostanes net production across the left anterior descending artery territory correlated with a decrease in superoxide dismutase activity (r=0.66, P=0.002) and decrease in coronary artery diameter in response to L-NMMA (r_s=0.48, P<0.05). Myeloperoxidase and nitrotyrosine gradients were similar in patients with endothelial dysfunction and controls. The effect of L-NMMA was similar in both groups. We conclude that coronary endothelial dysfunction in humans is characterized by local enhancement of oxidative stress without a decrease in basal NO release. This study supports the hypothesis that local oxidative stress has a role in reduction of NO bioavailability in humans with coronary endothelial dysfunction.

Key Words: endothelial function • oxidative stress • nitric oxide • acetylcholine