title: Redox-sensitive mechanism of no scavenging by nitronyl nitroxides.
abstract: Nitronyl nitroxides, NN., have been increasingly used in the field of NO-related studies as specific antagonists of NO. . We employed a combination of EPR and NMR spin trapping to study the mechanisms of the reaction of NN. with NO. in reducing environments. EPR allowed observation of NO-induced transformation of the paramagnetic trap, NN., to the corresponding iminonitroxide, IN. . In a complementary way, corresponding EPR-invisible diamagnetic products (the hydroxylamines NN-H and IN-H) were detected by 19F-NMR using newly synthesized fluorinated traps. Addition of reducing agents to a solution of NN. resulted in fast disappearance of its EPR spectra and appearance of a 19F-NMR peak of the corresponding hydroxylamine, NN-H. Addition of NO. as a bolus, or NO. generated on sodium nitroprusside photolysis, resulted in 19F-NMR-detectable accumulation of the hydroxylamine, IN-H. Upon high rates of NO. generation in ascorbate-containing solutions, partial recovery of NN. was observed, which undergoes further reactions with NO. and ascorbate in a competitive manner. Using 19F-NMR and a fluorinated trap, NO-induced conversion of NN-H into IN-H was also observed in vivo in hypertensive ISIAH rats compared with normotensive WAG rats. The results provide insight into a new potential redox-sensitive mechanism of the antagonistic action of NN. against NO., which may provide insight into previously unexplained behavior of this category of NO-reacting compounds.
authors.affiliation: Institute of Chemical Kinetics and Combustion, 630090, Novosibirsk, Russia.
authors.forename: Andrey A
authors.initials: AA
authors.lastname: Bobko
authors.forename: Elena G
authors.initials: EG
authors.lastname: Bagryanskaya
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Reznikov
authors.forename: Nataljya G
authors.initials: NG
authors.lastname: Kolosova
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Clanton
authors.forename: Valery V
authors.initials: VV
authors.lastname: Khramtsov
mesh_terms: D000818:Animals; D002531:Cerebellum; D003497:Cyclic N-Oxides / Q000378:metabolism / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000378:metabolism* / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000378:metabolism / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats; D019097:Spin Trapping
chemical_list: D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D007093:Imidazoles; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D009569:Nitric Oxide