Background:
Increased production of nitric oxide has been implicated as a mediator during septic shock and sepsis syndrome. Inhibition of nitric oxide production could be beneficial during endotoxemia to improve the individual's hemodynamic status and possibly outcome.
Objective:
To evaluate the effects of nitric oxide inhibition on macrophage function and survival in a murine sepsis model.
Design:
Sixty-eight female Swiss-Webster (ND4) mice were injected with a sublethal dose of Escherichia coli lipopolysaccharide (25 mg/kg).
Intervention:
The treated group (n=34) received 10 mg/kg of NG-nitro-l-arginine methyl ester at the time of lipopolysaccharide injection.
Main Outcome Measures:
Blood samples and peritoneal macrophages were obtained at baseline and at 2, 4, and 8 hours after injection. Nitrite levels were measured in 36 mice from plasma and supernatant samples of cultured peritoneal macrophages stimulated with interferon gamma (100 μg/mL) for 48 hours. Thirty-two animals were observed for survival.
Results:
Administration of N-nitro-l-arginine methyl ester after lipopolysaccharide injection caused significant reductions in macrophage mean nitrite production from 13 and 15 μmol/L to 7 and 11 μmol/L (P<.05) and reduced mean plasma nitrite concentrations from 100 and 118 μmol/L to 46 and 108 μmol/L (P<.05) at 2 and 4 hours, respectively. The rate of survival was significantly decreased to 0% in the group receiving N-nitro-l-arginine methyl ester after septic challenge compared with 87.5% in controls (P<.005).
Conclusion:
Inhibition of nitric oxide production is detrimental in this murine model of endotoxemia.(Arch Surg. 1994;129:142-148)