Vascular Free Radical Release Ex Vivo and In Vivo Evidence for a Flow-Dependent Endothelial Mechanism

Abstract Mechanisms underlying production of vascular free radicals are unclear. We hypothesized that changes in blood flow might serve as a physiological stimulus for endo-thelial free radical release. Intact isolated aortas from 45 rabbits were perfused with the spin trap a-phenyl-N-tert-butylnitrone (PBN, 20 mmol/L) and formed radical adducts detected by electron paramagnetic resonance spectroscopy (EPR). Sequential perfusion at 2, 7.5, and 12 mL/min changed cumulative vascular PBN radical adduct yields, respectively, from 3.2+0.9 to 4.1±0.7 (P<.05) and 7.0±1.5 (P<.005) pmol/mg with endothelium and from 3.6±1.6 to 3.8±1.4 and 2.2±0.8 pmol/mg without endothelium (P=NS). In endothe-lialized aortas, superoxide dismutase (SOD) completely blocked flow-induced free radical production, whereas inacti-vated SOD, indomethacin, and the nitric oxide synthetas