title: Impact of nitric-oxide-mediated vasodilation and oxidative stress on renal medullary oxygenation: a modeling study.
abstract: The goal of this study was to investigate the effects of nitric oxide (NO)-mediated vasodilation in preventing medullary hypoxia, as well as the likely pathways by which superoxide (O2(-)) conversely enhances medullary hypoxia. To do so, we expanded a previously developed mathematical model of solute transport in the renal medulla that accounts for the reciprocal interactions among oxygen (O2), NO, and O2(-) to include the vasoactive effects of NO on medullary descending vasa recta. The model represents the radial organization of the vessels and tubules, centered around vascular bundles in the outer medulla and collecting ducts in the inner medulla. Model simulations suggest that NO helps to prevent medullary hypoxia both by inducing vasodilation of the descending vasa recta (thus increasing O2 supply) and by reducing the active sodium transport rate (thus reducing O2 consumption). That is, the vasodilative properties of NO significantly contribute to maintaining sufficient medullary oxygenation. The model further predicts that a reduction in tubular transport efficiency (i.e., the ratio of active sodium transport per O2 consumption) is the main factor by which increased O2(-) levels lead to hypoxia, whereas hyperfiltration is not a likely pathway to medullary hypoxia due to oxidative stress. Finally, our results suggest that further increasing the radial separation between vessels and tubules would reduce the diffusion of NO towards descending vasa recta in the inner medulla, thereby diminishing its vasoactive effects therein and reducing O2 delivery to the papillary tip.
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina; and.
authors.forename: Brendan C
authors.initials: BC
authors.lastname: Fry
authors.affiliation: Sorbonne Universités, Université Pierre et Marie Curie (UPMC) Univ Paris 06, INSERM, Université Paris, Descartes, Sorbonne Paris Cité, UMRS 1138, ERL 8228, Centre de Recherche des Cordeliers, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Edwards
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina; and alayton@math.duke.edu.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D003198:Computer Simulation; D004058:Diffusion; D007679:Kidney Medulla / Q000098:blood supply* / Q000378:metabolism*; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010100:Oxygen / Q000097:blood*; D051381:Rats; D012079:Renal Circulation; D013481:Superoxides / Q000378:metabolism; D014664:Vasodilation
chemical_list: D013481:Superoxides; D009569:Nitric Oxide; D010100:Oxygen
keywords: hypoxia; mathematical model; oxygen; sodium transport
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