Activation of the cholinergic anti-inflammatory pathway reduces NF-kappab activation, blunts TNF-alpha production, and protects againts splanchic artery occlusion shock.

Abstract

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 + Sham STIM = 0% at 4 h of reperfusion; VGX + SAO + STIM = 90% at 4 h of reperfusion), reverted the marked hypotension, inhibited IkappaBalpha liver loss, blunted the augmented nuclear factor-kappaB activity, decreased hepatic tumor necrosis factor (TNF)-alpha mRNA (VGX + SAO + Sham STIM = 1.0 +/- 1.9 TNF-alpha/glyceraldehyde-3-phosphate dehydrogenase ratio; VGX + SAO + STIM = 0.3 +/- 0.2 TNF-alpha/glyceraldehyde-3-phosphate dehydrogenase ratio), reduced plasma TNF-alpha (VGX + SAO + Sham STIM = 118 +/- 19 pg/mL; VGX + SAO + STIM = 39 +/- 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 +/- 1 U/g tissue; VGX + SAO + STIM = 3.1 +/- 0.7 U/g tissue) and in the lung (VGX + SAO + Sham STIM = 8.0 +/- 1.0 U/g tissue; VGX + SAO + STIM = 3.2 +/- 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-kappaB and TNF-alpha in SAO shock.

• Authors: Domenica Altavilla, Salvatore Guarini, Alessandra Bitto, Chiara Mioni, Daniela Giuliani, Albertino Bigiani, Giovanni Squadrito, Letteria Minutoli, Francesco S Venuti, Francesco Messineo, Vincenzo De Meo, Carla Bazzani, Francesco Squadrito
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 25 Issue 5 Pg. 500-6 (May 2006) ISSN: 1073-2322 [Print] United States
• PMID: 16680015 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• I-kappa B Proteins
• NF-kappa B
• Nfkbia protein, rat
• Nicotinic Antagonists
• Receptors, Cholinergic
• Tumor Necrosis Factor-alpha
• NF-KappaB Inhibitor alpha
• Chlorisondamine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Arterial Occlusive Diseases (pathology)
• Chlorisondamine (pharmacology)
• Electric Stimulation
• I-kappa B Proteins (metabolism)
• Male
• NF-KappaB Inhibitor alpha
• NF-kappa B (metabolism)
• Nicotinic Antagonists (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Cholinergic (metabolism)
• Shock
• Splanchnic Circulation
• Tumor Necrosis Factor-alpha (metabolism)
• Vagus Nerve (pathology)