Nitronyl nitroxides as probes to study the mechanism of vasodilatory action of nitrovasodilators, nitrone spin traps, and nitroxides: role of nitric oxide

Free Radic Biol Med. 1995 Feb;18(2):169-77. doi: 10.1016/0891-5849(94)00112-w.

Abstract

Nitronyl nitroxides have been used to trap nitric oxide (.NO) produced during visible irradiation of nitrovasodilators such as sodium nitroprusside (Joseph et al., Biochem. Biophys. Res. Commun. 192:926-934; 1993). We have also shown that nitrone and nitroso spin traps exert a potent vasodilatory effect in the isolated perfused rat heart (Konorev et al., Free Radic. Biol. Med. 14:127-137, 1993). The objective of this study was to investigate the effect of nitronyl nitroxides on the vasodilatory action of sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy free radical (TEMPOL) in the isolated perfused rat heart model. In this study, we have used the following nitronyl nitroxides as nitric oxide traps: 2-(p-carboxyphenyl)-4,4,5,5-tetramethyl imidazoline-3-oxide 1-oxyl (SLI) and 2(1',1'-dimethyl-2'-hydroxyethyl)-4,4,5,5-tetramethyl imidazoline-3-oxide 1-oxyl (SLII). Under in vitro conditions, both SLI and SLII trapped .NO released from SNP/light treatment and from spontaneous decomposition of SNAP, forming the corresponding imino nitroxides, which were characterized by electron spin resonance (ESR) technique. In isolated hearts, SNP (2 mumol/l) and SNAP (20 mumol/l) increased coronary flow rate to a maximum of 185% and 190%, respectively. SNP-induced vasodilation was inhibited by SLI (0.05-3 mmol/l) from 162% to 131% of baseline, and SNAP-induced vasodilation was inhibited by SLII (0.05-1.2 mmol/l) from 190% to 136% of baseline. In contrast, neither SLI nor SLII inhibited the vasodilatory action elicited by POBN or TEMPOL.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Benzoates*
  • Coronary Circulation / drug effects
  • Cyclic N-Oxides / pharmacology*
  • Electron Spin Resonance Spectroscopy
  • Imidazoles / pharmacology
  • Male
  • Nitric Oxide / metabolism*
  • Nitrogen Oxides / pharmacology
  • Nitroprusside / pharmacology
  • Penicillamine / analogs & derivatives
  • Penicillamine / pharmacology
  • Pyridines
  • Rats
  • Rats, Sprague-Dawley
  • S-Nitroso-N-Acetylpenicillamine
  • Spin Labels*
  • Vasodilation / drug effects
  • Vasodilator Agents / pharmacology*

Substances

  • 2-(1',1'-dimethyl-2'-hydroxyethyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl
  • Benzoates
  • Cyclic N-Oxides
  • Imidazoles
  • Nitrogen Oxides
  • Pyridines
  • Spin Labels
  • Vasodilator Agents
  • alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone
  • 1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole
  • Nitroprusside
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Penicillamine
  • tempol