Objective: To investigate the effects of endogenous nitric oxide on hyperoxia and tumor necrosis factor-α-induced leukosequestration and proinflammatory cytokine release in rat airways. Design: Prospective, randomized, controlled animal study. Setting: Experimental laboratory. Subjects: Male Sprague-Dawley rats weighing 350-500 g. Interventions: The rats were pretreated with NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) or saline intravenously 4-6 mins before intratracheal administration of tumor necrosis factor-α, 95% oxygen, or both, when the vasopressor effect of L-NAME had reached a plateau. Measurements and Main Results: Bronchoalveolar lavage fluid was recovered from the airway of rats after exposure to 95% oxygen and tumor necrosis factor-α for 6 hrs under ventilator support. Neutrophils in lavage fluid were isolated and examined for the inducible nitric oxide synthase expression by flow-cytometric assay. Tumor necrosis factor-α and interleukin-1β in lavage fluid were measured by enzyme-linked immunosorbent assay. The percentage of neutrophils in bronchoalveolar fluid was significantly higher in rats exposed to hyperoxia + tumor necrosis factor-α (29.7 ± 12.5%) compared with rats with hyperoxia (16.3 ± 1.2%), tumor necrosis factor-α (4.2 ± 1.1%), or room air (5.0 ± 1.8%) alone (p < .05). Rats exposed to hyperoxia + tumor necrosis factor-α had significantly higher concentrations of inducible nitric oxide synthase of neutrophils (350.1 ± 75.7 mean fluorescence intensity), compared with rats with hyperoxia (64.9 ± 1.6 mean fluorescence intensity), tumor necrosis factor-α (102.6 ± 15.3 mean fluorescence intensity), or room air (111.2 ± 25.8 mean fluorescence intensity) alone (p < .05). Rats exposed to hyperoxia + tumor necrosis factor-α significantly produced higher concentrations of tumor necrosis factor-α and interleukin-1β, compared with rats with tumor necrosis factor-α, hyperoxia, or room air alone. Hyperoxia + tumor necrosis factor-α also significantly increased growth-related oncogene/cytokine-induced neutrophil chemoattractant (GRO/CINC)-1 in bronchoalveolar fluid, compared with those receiving tumor necrosis factor-α alone, hyperoxia alone, or room air alone. L-NAME significantly enhanced the percentage of neutrophil recovery and the production of tumor necrosis factor-α, interleukin-1β, and GRO/CINC-1 in airways compared with the corresponding hyperoxia + tumor necrosis factor-α treatment alone. Conclusions: Endogenous nitric oxide may be an important endogenous inhibitor of hyperoxia + tumor necrosis factor-α-induced leukocyte recruitment and subsequently tumor necrosis factor-α, interleukin-1β, and GRO/CINC-1 release.
|頁（從 - 到）||508-516|
|期刊||Critical Care Medicine|
|出版狀態||已發佈 - 二月 1 2003|
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine