Activation of the cholinergic anti-inflammatory pathway reduces NF-kappa B activation, blunts TNF-alpha production, and protects against splanchnic artery occlusion shock

The cholinergic anti-inflammatory pathway has not yet been studied in splanchnic artery occlusion (SAO) shock. We investigated whether electrical stimulation (STIM) of efferent vagus nerves suppresses the inflammatory cascade in SAO shock. Animals were subjected to clamping of the splanchnic arteries for 45 min, followed by reperfusion. This surgical procedure resulted in an irreversible state of shock (SAO shock). Sham-operated animals were used as controls. Two minutes before the start of reperfusion, rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Application of constant voltage pulses to the caudal vagus ends (STIM: 5 V, 2 ms, 6 Hz for 15 min, 5 min after the beginning of reperfusion) increased survival rate (VGX + SAO+ ShamSTIM= 0% at 4 h of reperfusion; VGX + SAO+ STIM = 90%at 4 h of reperfusion), reverted the marked hypotension, inhibited I.B! liver loss, blunted the augmented nuclear factor-.B activity, decreased hepatic tumor necrosis factor (TNF)-! mRNA (VGX + SAO + Sham STIM = 1.0 T 1.9 TNF-!/ glyceraldehyde-3-phosphate dehydrogenase ratio; VGX + SAO + STIM = 0.3 T 0.2 TNF-!/glyceraldehyde-3-phosphate dehydrogenase ratio), reduced plasma TNF-! (VGX + SAO + Sham STIM = 118 T 19 pg/mL; VGX + SAO + STIM = 39 T 8 pg/mL), ameliorated leukopenia, and decreased leukocyte accumulation, as revealed by means of myeloperoxidase activity in the ileum (VGX + SAO + Sham STIM = 7.9 T 1 U/g tissue; VGX + SAO + STIM = 3.1 T 0.7 U/g tissue) and in the lung (VGX + SAO + Sham STIM = 8.0 T 1.0 U/g tissue; VGX + SAO + STIM = 3.2 T 0.6 U/g tissue). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation. Our results show a parasympathetic inhibition of nuclear factor-.B and TNF-! in SAO shock.