title: Nitronyl nitroxides as probes to study the mechanism of vasodilatory action of nitrovasodilators, nitrone spin traps, and nitroxides: role of nitric oxide.
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)
authors.affiliation: Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Konorev
authors.forename: M M
authors.initials: MM
authors.lastname: Tarpey
authors.forename: J
authors.initials: J
authors.lastname: Joseph
authors.forename: J E
authors.initials: JE
authors.lastname: Baker
authors.forename: B
authors.initials: B
authors.lastname: Kalyanaraman
mesh_terms: D000818:Animals; D001565:Benzoates; D003326:Coronary Circulation / Q000187:drug effects; D003497:Cyclic N-Oxides / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011725:Pyridines; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D013113:Spin Labels; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: C093502:2-(1',1'-dimethyl-2'-hydroxyethyl)-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl; D001565:Benzoates; D003497:Cyclic N-Oxides; D007093:Imidazoles; D009589:Nitrogen Oxides; D011725:Pyridines; D013113:Spin Labels; D014665:Vasodilator Agents; C043438:alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; C001803:tempol