Effect of an imidazolineoxyl nitric oxide on prostaglandin synthesis in experimental shock: Possible role of nitrogen dioxide in prostacyclin synthase inactivation

The effect of 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-o xide (cPTIO), a nitric oxide (NO) scavenger that yields nitrogen dioxide (N O2) in a rat endotoxemia model was investigated. Endotoxin (lipopolysacchar ide [LPS]) increased NO synthase (NOS) activity and inducible NOS expressio n measured in lung and plasma levels of nitrite/nitrate, 6-oxoprostaglandin (PG) F-1 alpha, thromboxane B-2, and PGF(2 alpha). Infusion of cPTIO signi ficantly reduced LPS-induced mean arterial blood pressure decline and morta lity and selectively reduced LPS-induced 6-oxo-PGF(1 alpha) plasma levels a nd prostacyclin synthase (PGIS) activity measured in the lung and aorta. In vitro, PGIS activity in aorta rings was not modified by SNAP (NO donor), c PTIO slightly inhibited the enzyme but not in the presence of L-N-G-monomet hyl arginine, and SNAP in combination with cPTIO significantly inhibited PG IS. Thus, cPTIO may be beneficial in endotoxic shock because of NO scavengi ng and PGIS inactivation, which could be mediated by NO2.