Modeling the influence of superoxide dismutase on superoxide and nitric oxide interactions, including reversible inhibition of oxygen consumption.
A mathematical mass transport model was constructed in cylindrical geometry to follow coupled biochemical reactions and diffusion of oxygen, nitric oxide, superoxide, peroxynitrite, hydrogen peroxide, nitrite, and nitrate around a blood vessel. Computer simulations were performed for a 50 microm internal diameter arteriole to characterize mass transport in five concentric regions (blood, plasma layer, endothelium, vascular wall, perivascular tissue). Steady state gradients in nitric oxide, oxygen partial pressure, superoxide, and peroxynitrite, and associated production of hydrogen peroxide, nitrite, and nitrate were predicted for varying superoxide production rates, superoxide dismutase concentrations, and other physiological conditions. The model quantifies how competition between superoxide scavenging by nitric oxide and superoxide dismutase catalyzed removal varies spatially. Reversible inhibition of oxygen consumption by nitric oxide, which causes increased tissue oxygenation at deeper locations, was also included in the model. The mass transport model provides insight into complex interactions between reactive oxygen and nitrogen species in blood and tissue, and provides an objective way to evaluate the relative influence of different biochemical pathways on these interactions.
Buerk
Donald G
DG
Department of Physiology, B400 Richards Building, University of Pennsylvania, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA. buerk@seas.upenn.edu
Lamkin-Kennard
Kathleen
K
Jaron
Dov
D
D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D001808:Blood Vessels / Q000378:metabolism*; D003198:Computer Simulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008962:Models, Theoretical; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D010101:Oxygen Consumption; D030421:Peroxynitrous Acid / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*
D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D005609:Free Radicals; D009566:Nitrates; D009573:Nitrites; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D006861:Hydrogen Peroxide; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase