alpha-(4-pyridyl-1-oxide)-n-tert-butylnitrone and 1-3-dihydroxy-4-4-5-5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole

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)

Topics: Animals; Benzoates; Coronary Circulation; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; Imidazoles; Male; Nitric Oxide; Nitrogen Oxides; Nitroprusside; Penicillamine; Pyridines; Rats; Rats, Sprague-Dawley; S-Nitroso-N-Acetylpenicillamine; Spin Labels; Vasodilation; Vasodilator Agents