Superoxide dismutase impact on nitric oxide levels in the microcirculation‐ a mathematical model

Abstract

Interactions of free radicals including superoxide, nitric oxide (NO), and peroxynitrite are important in pathophysiological conditions such as hypertension, atherosclerosis, diabetes and cardiovascular disease. Excess levels of superoxide resulting from oxidative stress cause reduction in NO bioavailability in these conditions, which results in endothelial dysfunction. Extracellular superoxide dismutase (ecSOD) may regulate the bioavailability of NO by competing for superoxide, thus restricting the formation of peroxynitrite. We developed a mathematical model of free radical transport within and around an arteriole vessel during oxidative stress, based on fundamental principles of mass balance, reaction kinetics, and vascular geometry. The model investigates the NO interactions with superoxide and peroxynitrite and the interaction of ecSOD with superoxide. The model results indicate that ecSOD location and concentration in the arteriolar vessel significantly affect superoxide concentration. The model predicted that a reduction in ecSOD results in increased superoxide and peroxynitrite concentrations and decreased NO concentration in arteriolar vessel. Model results suggest a role of ecSOD in amelioration of oxidative stress and NO bioavailability in the microcirculation. The results will further our understanding of endothelial dysfunction in physiological and pathophysiological conditions and the impact of ecSOD on the free radical interactions. Supported by American Heart Association SDG 0530050N, and Arkansas Biosciences Institute (ABI)