ACTIVATION OF THE CHOLINERGIC ANTI-INFLAMMATORY PATHWAY REDUCES NF-κB ACTIVATION, BLUNTS TNF-α PRODUCTION, AND PROTECTS AGAINTS SPLANCHIC ARTERY OCCLUSION SHOCK
Open accessAbstract
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.
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“Pretreatment with the irreversible nicotinic acetylcholine receptor antagonist chlorisondamine (16) did not modify survival in SAOshocked rats but prevented the protective effect of vagal stimulation on survival rate and time (74 T 5 min; Table 1).”
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- Authors
- Altavilla, D., Guarini, S., Bitto, A., Mioni, C., Giuliani, D., Bigiani, A., Squadrito, G., Minutoli, L., Venuti, F. S., Messineo, F., De Meo, V., Bazzani, C., & Squadrito, F.
- Affiliations
- University of Messina (IT)
- University of Modena and Reggio Emilia (IT)
- Corresponding author
- Altavilla, Domenica
- Bitto, Alessandra
- Minutoli, Letteria
- Squadrito, Francesco
- ORCID
- Venue
- Shock
- Published
- 2006-05
- Volume
- 25
- Issue
- 5
- Pages
- 500-506
- ISSN
- 1073-2322 (ISSN-L)
- OpenAlex
- W2093497877
- Cited by
- 98
- References
- 27
- Citations by year
- 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2018: 8 · 2017: 5 · 2016: 2 · 2015: 4 · 2014: 6 · 2013: 3 · 2012: 6
- FWCI
- 5.04
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by
- Locations
- Shock (publishedVersion)
- PubMed (publishedVersion)
- IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- cholinergic anti-inflammatory pathway, vagus nerve stimulation, NF-κB activation, TNF-α, IκBα, vagotomy, ischemia-reperfusion injury, leukocyte accumulation, myeloperoxidase, hypotension, inflammatory cytokines, lung, ileum, survival rate, leukopenia
- MeSH terms
- NF-KappaB Inhibitor alpha, Animals, Anti-Inflammatory Agents, Arterial Occlusive Diseases, Chlorisondamine, Electric Stimulation, Male, Receptors, Cholinergic, Shock, Splanchnic Circulation, Tumor Necrosis Factor-alpha, Vagus Nerve, NF-kappa B, Rats, Sprague-Dawley, Nicotinic Antagonists, I-kappa B Proteins, Rats
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