Redox-sensitive mechanism of no scavenging by nitronyl nitroxides

Free Radic Biol Med. 2004 Jan 15;36(2):248-58. doi: 10.1016/j.freeradbiomed.2003.10.022.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebellum
  • Cyclic N-Oxides / metabolism
  • Cyclic N-Oxides / pharmacology
  • Electron Spin Resonance Spectroscopy
  • Free Radical Scavengers / metabolism*
  • Free Radical Scavengers / pharmacology*
  • Hydrogen-Ion Concentration
  • Imidazoles / metabolism
  • Imidazoles / pharmacology
  • Magnetic Resonance Spectroscopy
  • Nitric Oxide / analysis
  • Nitric Oxide / metabolism*
  • Oxidation-Reduction
  • Rats
  • Spin Trapping

Substances

  • Cyclic N-Oxides
  • Free Radical Scavengers
  • Imidazoles
  • 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
  • Nitric Oxide