Cited by 131Vagus Nerve Stimulation ResearchNeuropeptides and Animal PhysiologyTrauma, Hemostasis, Coagulopathy, Resuscitation

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Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway

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GUARINI, S·2004·Cardiovascular Research

DOI 10.1016/j.cardiores.2004.03.029

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Abstract

OBJECTIVE: Several melanocortin peptides have a prompt and sustained resuscitating effect in conditions of hemorrhagic shock. The transcription nuclear factor kappaB (NF-kappaB) triggers a potentially lethal systemic inflammatory response, with marked production of tumor necrosis factor-alpha (TNF-alpha), in hemorrhagic shock. Here we investigated whether the hemorrhagic shock reversal produced by the melanocortin ACTH-(1-24) (adrenocorticotropin) depends on the activation of the recently recognized, vagus nerve-mediated, brain "cholinergic anti-inflammatory pathway". METHODS AND RESULTS: Anesthetized rats were stepwise bled until mean arterial pressure (MAP) stabilized at 20-25 mm Hg. The severe hypovolemia was incompatible with survival, and all saline-treated animals died within 30 min. In rats intravenously (i.v.) treated with ACTH-(1-24), neural efferent activity along vagus nerve (monitored by means of a standard system for extracellular recordings) was markedly increased, and the restoration of cardiovascular and respiratory functions was associated with blunted NF-kappaB activity and with decreased TNF-alpha mRNA liver content and TNF-alpha plasma levels. Bilateral cervical vagotomy, pretreatment with the melanocortin MC(4) receptor antagonist HS014, atropine sulfate or chlorisondamine, but not with atropine methylbromide, prevented the life-saving effect of ACTH-(1-24) and the associated effects on NF-kappaB activity and TNF-alpha levels. HS014 and atropine sulfate prevented, too, the ACTH-(1-24)-induced increase in neural efferent vagal activity, and accelerated the evolution of shock in saline-treated rats. CONCLUSIONS: The present data show, for the first time, that the melanocortin ACTH-(1-24) suppresses the NF-kappaB-dependent systemic inflammatory response triggered by hemorrhage, and reverses shock condition, by brain activation (in real-time) of the "cholinergic anti-inflammatory pathway", this pathway seeming to be melanocortin-dependent.

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Authors: GUARINI, S.
Affiliations: University of Modena and Reggio Emilia (IT)
Corresponding author: GUARINI, S
ORCID: GUARINI, S
Venue: Cardiovascular Research
Publisher: Oxford University Press (OUP)
Published: 2004-08
Volume: 63
Issue: 2
Pages: 357-365
ISSN: 0008-6363 (ISSN-L)
DOI: 10.1016/j.cardiores.2004.03.029
OpenAlex: W2122677936
Cited by: 131
References: 42
Citations by year: 2026: 2 · 2025: 1 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 7 · 2016: 4 · 2015: 9 · 2014: 7 · 2013: 7 · 2012: 12
FWCI: 5.01
Type: journal article
Language: en
Update notices: expression_of_concern (2023-03-01)
Open access: bronze
doi.org
Locations: Cardiovascular Research (publishedVersion)
PubMed (publishedVersion)
IRIS UNIMORE (University of Modena and Reggio Emilia) (submittedVersion, cc-by)
Funders: Ministero dell’Istruzione, dell’Università e della Ricerca
National Institutes of Health
Topics: Life Sciences › Neuroscience › Neurology › Vagus Nerve Stimulation Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Trauma, Hemostasis, Coagulopathy, Resuscitation
Keywords: ACTH, ACTH1-24, hemorrhagic shock, cholinergic anti-inflammatory pathway, vagus nerve, NF-κB, TNF-α, systemic inflammatory response, vagotomy, hypovolemia, resuscitation
MeSH terms: Acute Disease, Animals, Atropine, Chlorisondamine, Cosyntropin, Female, Liver, Male, Receptors, Nicotinic, RNA, Messenger, Shock, Hemorrhagic, Tumor Necrosis Factor-alpha, Vagus Nerve, NF-kappa B, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, I-kappa B Proteins, Electrophoretic Mobility Shift Assay, Rats

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Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway

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