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-oxide (cPTIO), a nitric oxide (NO) scavenger that yields nitrogen dioxide (NO(2)) in a rat endotoxemia model was investigated. Endotoxin (lipopolysaccharide [LPS]) increased NO synthase (NOS) activity and inducible NOS expression measured in lung and plasma levels of nitrite/nitrate, 6-oxo-prostaglandin (PG) F(1alpha), thromboxane B(2), and PGF(2alpha). Infusion of cPTIO significantly reduced LPS-induced mean arterial blood pressure decline and mortality and selectively reduced LPS-induced 6-oxo-PGF(1alpha) plasma levels and prostacyclin synthase (PGIS) activity measured in the lung and aorta. In vitro, PGIS activity in aorta rings was not modified by SNAP (NO donor), cPTIO slightly inhibited the enzyme but not in the presence of L-N(G)-monomethyl arginine, and SNAP in combination with cPTIO significantly inhibited PGIS. Thus, cPTIO may be beneficial in endotoxic shock because of NO scavenging and PGIS inactivation, which could be mediated by NO(2).
Soler
M
M
Laboratory of Inflammation Mediators, Institute of Research of Santa Creu i Sant Pau Hospital, Barcelona, Spain.
Camacho
M
M
Molins-Pujol
A M
AM
Vila
L
L
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001565:Benzoates / Q000494:pharmacology*; D046508:Culture Techniques; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy*; D007093:Imidazoles / Q000494:pharmacology*; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008070:Lipopolysaccharides; D008168:Lung / Q000378:metabolism; D008297:Male; D009566:Nitrates / Q000097:blood; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001565:Benzoates; D065607:Cytochrome P-450 Enzyme Inhibitors; D007093:Imidazoles; D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D011453:Prostaglandins; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D019001:Nitric Oxide Synthase; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D009585:Nitrogen Dioxide