title: A mathematical model for the role of N2O3in enhancing nitric oxide bioavailability following nitrite infusion.
abstract: Nitrite infusion into the bloodstream has been shown to elicit vasodilation and protect against ischemia-reperfusion injury through nitric oxide (NO) release in hypoxic conditions. However, the mechanism by which nitrite-derived NO escapes scavenging by hemoglobin in the erythrocyte has not been fully elucidated, owing in part to the difficulty in measuring the reactions and transport on NO in vivo. We developed a mathematical model for an arteriole and surrounding tissue to examine the hypothesis that dinitrogen trioxide (N2O3) acts as a stable intermediate for preserving NO. Our simulations predict that with hypoxia and moderate nitrite concentrations, the N2O3pathway can significantly preserve the NO produced by hemoglobin nitrite reductase in the erythrocyte and elevate NO reaching the smooth muscle cells. Nitrite retains its ability to increase NO bioavailability even at varying flow conditions, but there is minimal effect under normoxia or very low nitrite concentrations. Our model demonstrates a viable pathway for reconciling experimental findings of potentially beneficial effects of nitrite infusions despite previous models showing negligible NO elevation associated with hemoglobin nitrite reductase. Our results suggest that additional mechanisms may be needed to explain the efficacy of nitrite-induced vasodilation at low infusion concentrations.
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors: Yien
authors: Y
authors: Liu
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors: Donald G
authors: DG
authors: Buerk
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA.
authors: Kenneth A
authors: KA
authors: Barbee
authors: School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St., Philadelphia, PA 19104, USA. Electronic address: dov.jaron@drexel.edu.
authors: Dov
authors: D
authors: Jaron
mesh_terms: D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism*; D001682:Biological Availability; D001783:Blood Flow Velocity; D000860:Hypoxia / Q000378:metabolism*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D009573:Nitrites / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000378:metabolism* / Q000493:pharmacokinetics; D010100:Oxygen / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D009573:Nitrites; D009589:Nitrogen Oxides; C031701:nitrogen trioxide; D009569:Nitric Oxide; D010100:Oxygen
keywords: Arteriole; Dinitrogen trioxide; Hypoxic vasodilation; Nitrite infusion; Nitrous anhydride