Nitronyl nitroxides as probes to study the mechanism of vasodilatory action of nitrovasodilators, nitrone spin traps, and nitroxides: role of nitric oxide.
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)
Konorev
E A
EA
Biophysics Research Institute, Medical College of Wisconsin, Milwaukee 53226, USA.
Tarpey
M M
MM
Joseph
J
J
Baker
J E
JE
Kalyanaraman
B
B
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*
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