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Effect of Reactive Oxygen Metabolites on Endothelial Permeability: Role of Nitric Oxide and Iron
Author(s) -
OKAYAMA NAOTSUKA,
GRISHAM MATTHEW B.,
KEVIL CHRISTOPHER G.,
EPPIHIMER LOIS ANN,
WINK DAVID A.,
ALEXANDER J. STEVEN
Publication year - 1999
Publication title -
microcirculation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.793
H-Index - 83
eISSN - 1549-8719
pISSN - 1073-9688
DOI - 10.1111/j.1549-8719.1999.tb00093.x
Subject(s) - xanthine oxidase , chemistry , nitric oxide , superoxide , hydrogen peroxide , superoxide dismutase , peroxynitrite , catalase , radical , xanthine , peroxide , reactive oxygen species , hydroxyl radical , biochemistry , biophysics , antioxidant , organic chemistry , enzyme , biology
Objective : We evaluated the effects of the xanthine oxidase (XO)‐derived reactive oxygen metabolites on the permeability of bovine pulmonary arteryendothelial monolayers and examined how iron and nitric oxide (NO) participate in these changes in permeability. Methods : Permeability was measured using a cell‐column chromatographic method in which monolayers were exposed to combinations of agents. Results : Exposure of monolayers to a superoxide/peroxide generator, xanthine (X, 0.1 mM)/XO (25 mU/mL), increased solute permeability after 10 minutes, but the same dose of either X or XO alone did not. Exposure of monolayers to peroxide (0.1 mM) also increased permeability, but only after 70 minutes. This X/XO permeability was attenuated by either catalase, superoxide dismutase, methionine (1 mM), an oxy‐radical scavenger, or desferrioxamine (0.1 mM), an iron chelator. Spermine NONOate (SNO), an NO donor, attenuated X/XO permeability at 0.1 mM, but this protection was not significant at 0.01 or 1 mM. Spermine NONOate (0.1 mM) did not alter the permeability produced by 0.1 mM peroxide. L‐ N 5 ‐(1‐iminoethyl)‐ornithine (10 µM), an NO synthase inhibitor, completely blocked peroxide‐, and partially attenuated X/XO‐mediated permeability. However, 3‐morphosynodiomine (SIN‐1, 1 mM) plus catalase (1,000 U/mL), a peroxynitrite generator, did not alter permeability. Conclusions : Xanthine/Xanthine Oxidase permeability involves peroxide, superoxide, oxy‐radicals, and iron. Endogenous NO may regulate peroxide‐, but not superoxide‐mediated permeability. The protective effects of exogenous NO on the X/XO permeability may represent interactions between superoxide, peroxide, and cell surface‐bound iron.