A. Baykal et al., Experimental study of the effect of nitric oxide inhibition on mesenteric blood flow and interleukin-10 levels with a lipopolysaccharide challenge, WORLD J SUR, 24(9), 2000, pp. 1116-1120
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.