Soler M, Camacho M, Molins-Pujol A M, Vila L
Laboratory of Inflammation Mediators, Institute of Research of Santa Creu i Sant Pau Hospital, Barcelona, Spain.
J Infect Dis. 2001 Jan 1;183(1):105-12. doi: 10.1086/317639. Epub 2000 Nov 10.
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).
研究了2-(4-羧基苯基)-4,4,5,5-四甲基咪唑啉-1-氧基-3-氧化物（cPTIO）在大鼠内毒素血症模型中的作用，cPTIO是一种一氧化氮（NO）清除剂，可产生二氧化氮（NO₂）。内毒素（脂多糖[LPS]）增加了肺和血浆中亚硝酸盐/硝酸盐、6-氧代前列腺素（PG）F₁α、血栓素B₂和PGF₂α水平所测得的一氧化氮合酶（NOS）活性和诱导型NOS表达。输注cPTIO可显著减轻LPS诱导的平均动脉血压下降和死亡率，并选择性降低LPS诱导的肺和主动脉中所测得的血浆6-氧代-PGF₁α水平和前列环素合酶（PGIS）活性。在体外，一氧化氮供体（SNAP）未改变主动脉环中的PGIS活性，cPTIO轻微抑制该酶，但在L-N(G)-单甲基精氨酸存在时则不然，且SNAP与cPTIO联合使用可显著抑制PGIS。因此，cPTIO可能因清除NO和使PGIS失活而对内毒素休克有益，这可能由NO₂介导。
