Experimental study of the effect of nitric oxide inhibition on mesenteric blood flow and interleukin-10 levels with a lipopolysaccharide challenge

The septic shock-induced decrease in mesenteric blood flow and release of p roinflammatory cytokines are among the major pathophysiologic changes presu med to lead to multiple organ dysfunction syndrome (MODS). Increased nitric oxide (NO) levels are associated with both decreased mesenteric blood how and positive modulation of proinflammatory cytokine release. In this study we aimed to determine the effect of the timing of the inhibition of nitric oxide synthase (NOS) on mesenteric blood flow and serum interleukin-10 (IL- 10) concentrations during endotoxin shock. A nonspecific NOS inhibitor N-G- nitro-L-arginine methyl ester (L-NAME), a specific NOS inhibitor aminoguani dine (AG), or placebo were injected 20 minutes before or 20 minutes after a lipopolysaccharide (LPS) or placebo challenge to Swiss-albino mice, as pre treatment or posttreatment, respectively. At 120 minutes after LPS or place bo injection the mesenteric blood how was measured, and blood samples from the heart were obtained for IL-10 levels in both groups. Pretreatment and p osttreatment with both NOS inhibitors prevented the LPS-induced decrease in mesenteric blood flow. Pretreatment was more effective for this purpose. P retreatment accentuated the LPS-induced increase in serum IL-10 concentrati ons, whereas posttreatment had no significant effect. We conclude that the timing of NOS inhibition is important for attenuating some deleterious effe cts of endotoxin.