Mathematical and computational models of oxidative and nitrosative stress

The importance of nitric oxide (NO), superoxide (O2-), and peroxynitrite (ONOO-), interactions in physiologic functions and pathophysiological conditions such as cardiovascular disease, hypertension, and diabetes have been established extensively in in vivo and in vitro studies. Despite intense investigation of NO, O2-, and ONOO- biochemical interactions, fundamental questions regarding the role of these molecules remain unanswered. Mathematical models based on fundamental principles of mass balance and reaction kinetics have provided significant results in the case of NO. However, the models that include interaction of NO, O2-, and ONOO- have been few because of the complexity of these interactions. Not only do these mathematical and computational models provided quantitative knowledge of distributions and concentrations of NO, O2-, and ONOO- under normal physiologic and pathophysiologic conditions, they also can help to answer specific hypotheses. The focus of this review article is on the models that involve more than one of the 3 molecules (NO, O2-, and ONOO-). Specifically, kinetic models of O2- dismutase and tyrosine nitration and biotransport models in the microcirculation are reviewed. In addition, integrated experimental and computational models of dynamics of NO/O2-/ONOO- in diverse systems are reviewed.