Impact of Superoxide Dismutase on Nitric Oxide and Peroxynitrite Levels in the Microcirculation - A Computational Model

Interactions of free radicals such as superoxide (O₂ ^-), nitric oxide (NO), and peroxynitrite (ONOO") are important in pathophysiological conditions such as hypertension, atherosclerosis, diabetes and the resulting cardiovascular diseases. Excessive levels of superoxide during oxidative stress cause a reduction in NO bioavailability by forming peroxynitrite and resulting in endothelial dysfunction. Superoxide dismutase (SOD) competes with NO for superoxide, and reduces the formation of peroxynitrite. In this study, we developed a mathematical model for free radical transport within and around an arteriolar vessel based on the fundamental principles of mass balance, reaction kinetics, and vascular geometry. We used the model to study the effect of the three types of SOD, viz. CuZn-SOD, Mn-SOD and extra cellular-SOD, on the bioavailability of NO. Results indicate that SOD location and concentration in the arteriole significantly affect superoxide concentration. The model predicts that a reduction in SOD levels results in increased superoxide and peroxynitrite concentrations and decreased NO concentration in the vessel. The results also suggest a role of SOD in the amelioration of oxidative stress and NO bioavailability in microcirculation. This model will help in furthering our knowledge of endothelial dysfunction in pathological conditions and the impact of specific SODs on free radical interactions.