CORONARY REACTIVITY AND OXIDATIVE STRESS

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DESCRIPTION: This is a resubmitted grant application to study endothelium- dependent relaxation in the coronary circulation of patients with coronary atherosclerosis. The application emphasizes the relationship of abnormalities in redox state and the generation and release of EDRF in these patients. Endothelium-dependent vasomotion will be studied in response to infusions of acetylcholine and substance P and increased blood flow during cardiac pacing. Vasomotor responses will assessed using intracoronary Doppler and quantitative angiography. These responses will be related to markers of antioxidant protection and oxidative stress in the coronary vasculature (coronary sinus concentrations of F2-isoprostanes and endothelin) and the systemic circulation (plasma antioxidant content and LDL susceptibility to oxidation). To examine the contribution of superoxide production to abnormal coronary activity, vasomotor responses will be examined following treatment with specific inhibitors of superoxide action.