Antagonistic action of imidazolineoxyl N-oxides against endothelium-derived relaxing factor/.NO through a radical reaction.

摘要: A labile inorganic free radical, nitric oxide (.NO), is produced by synthase from the substrate L-arginine in various cells and tissues. It acts as an endothelium-derived relaxing factor (EDRF) or a neurotransmitter vivo. We investigated reactivity of stable radical compounds, imidazolineoxyl N-oxides such 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO), carboxy-PTIO, carboxymethoxy-PTIO against .NO/EDRF both chemical biological systems. By using electron spin resonance (ESR) spectroscopy, were found to react with .NO stoichiometric manner (PTIO/.NO = 1.0) neutral solution (sodium phosphate buffer, pH 7.4) rate constants approximately 10(4) M-1 s-1, resulting generation NO2-/NO3- imidazolineoxyls (PTI), carboxy-PTI, carboxymethoxy-PTI. Furthermore, effects on acetylcholine- ATP-induced relaxation smooth muscle rabbit aorta tested. The vasorelaxations inhibited all three markedly. inhibitory carboxy-PTIO was almost 2-fold stronger than those synthesis inhibitors, N omega-nitro-L-arginine omega-monomethyl-L-arginine. Generation EDRF/.NO identified reacting PTIO aortic strips quantitating reaction product ESR spectroscopy. Thus, it clarified that N-oxide antagonize via unique radical-radical .NO.