Role of Reactive Oxygen Species in the Microcirculation

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All cells of vascular tissue including endothelial cells, and smooth muscle cells have enzyme systems that produce reactive oxygen species (ROS). Important ROS generated in the vascular tissue are superoxide or hydrogen peroxide. Superoxide can react with endothelium-derived nitric oxide (NO) to form peroxynitrite. Antioxidant systems protect against damage from ROS in normal physiological conditions. When ROS generation overwhelms the antioxidant defense (known as oxidative stress), these radicals can alter cellular function by interacting with DNA, RNA, and fatty acids, contribute to impairment of endothelium-dependent vasodilation and lead to apoptosis. We formulated a detailed computational model of NO, superoxide and peroxynitrite transport in a tissue containing an arteriolar blood vessel to quantify these species biochemical interactions and transport in the microcirculation. In this study, we analyzed compartmentalization and localization of superoxide formation and resulting tyrosine nitration formation. The model predicted that NO, superoxide and peroxynitrite levels and resulting tyrosine nitration are affected by a number of factors including the location and extent of oxidative stress. The model predictions provide insightinto role of individual forms of superoxide dismutase in physiologic and disease conditions. The results are significant because tyrosine nitration is observed in many pathological conditions but cellular sources for superoxide varies in different disease states. Supported by American Heart Association National SDG #0530050N and Arkansas Biosciences Institute (ABI).