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)-N-.) 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-nitraso-N-acetylpenicillamine (SNAP), alpha-(4-pyridyl-1-oxide)-N-tert-butyl nitrone (POBN) and 4-hydroxy-2,2,6,6-tetramethylpiperidinyl 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)-N-. 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 mu mol) and SNAP (20 mu mol/l) increased coronary how 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. Only SNP and SNAP, but not POBN and TEMPOL, increased the cyclic GMP release into the coronary effluent. We conclude that coronary vascular relaxation induced by SNP and SNAP is mediated by (NO)-N-. and that the mechanism of the vasodilatory effect of POBN and TEMPOL does not involve (NO)-N-. release.