Abstract 10321: Oral Atorvastatin Treatment Improves NO Bioavailability and Vascular Redox State in the Human Arterial Wall, via a Tetrahydrobiopterin-Mediated Improvement of eNOS Coupling

Background: The exact mechanisms by which statins affect endothelial nitric oxide synthase (eNOS) biology in human atherosclerosis are unclear. We hypothesized that statin treatment improves nitric oxide (NO) bioavailability reduces arterial superoxide (O2-) generation in human arterial wall by modifying eNOS coupling via a tetrahydrobiopterin (BH4)-mediated mechanism. Methods: In Study 1, in 492 patients undergoing CABG, endothelial function was evaluated by flow-mediated dilation in the brachial artery (FMD) and by ex-vivo vasomotor studies of saphenous veins (SV), while vascular O2- was determined in mammary arteries (IMA) by lucigenin chemiluminescence. In Study 2, 42 patients undergoing CABG were randomized to receive atorvastatin 40mg/day or placebo for 3 days preoperatively. FMD was determined at baseline and before CABG, while IMAs were used to measure arterial O2- and …