A computational model for analysis of SOD isoforms impact on nitric oxide biotransport in an arteriole

Abstract

Interactions of free radicals including superoxide (O2−), nitric oxide (NO), and peroxynitrite (ONOO−) are important in pathophysiological conditions such as hypertension, atherosclerosis, diabetes and cardiovascular disease. Excess levels of O2− in oxidative stress cause reduction in NO bioavailability, which results in endothelial dysfunction. The bioavailability of NO is affected by SOD which scavenges O2− and restricts ONOO− formation. There are three isoforms of SOD in present in the microcirculation, CuZn-SOD, EC-SOD and Mn-SOD, each with distinct contributions to maintaining the oxidative state in the microcirculation. 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 role of SOD isoforms in maintaining NO bioavailability, oxidative state and ONOO− formation. The model results indicate that SOD type, location and concentration in the arteriolar vessel significantly affect O2− levels. The model predicted that a reduction in SOD results in increased O2− and ONOO− levels and decreased NO levels in arteriolar vessel. The results will further our understanding of endothelial dysfunction in physiological and pathophysiological conditions and the importance of SOD isoforms in free radical interactions. Supported by American Heart Association SDG 0530050N, and Arkansas Biosciences Institute (ABI)