PTIO

PTIO, 2-phenyl-4,4,5,5-tetramethylimidazolineoxyl-1-oxyl-3-oxide, is a stable radical compound used to scavenge and trap NO radicals. The reaction between PTIO and NO produces NO₂ and derivatives of 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl. This reaction can be monitored with ESR spectroscopy. PTIO and its water soluble derivative Carboxy-PTIO are demonstrated to block many biological actions mediated by NO. PTIO reaction with NO is described to suppress the pathogenicity of excessively produced NO in endotoxin shock and to inhibit endothelium-dependent vascular relaxation mediated by NO in an ex vivo system. The vasorelaxant effects of NO on rabbit aorta smooth muscle was inhibited by both PTIO compounds and Carboxy-PTIO was shown to inhibit vasorelaxation almost two-fold more strongly than by inhibitors of NO synthesis N-ω-nitro-L-arginine and N-ω-monomethyl-L-arginine. NO-induced enhancement of tumor vascular permeability was also blocked by the PTIO compounds. The PTIO radical compounds directly extinguish cellular NO without affecting the activity of NOS (nitric acid synthase), distinguishing this mechanism of action from other methods of NO perturbation.