Adrenocorticotropin reverses hemorrhagic shock in anesthetized rats through the rapid activation of a vagal anti-inflammatory pathway
| Autor: | Herbert Marini, Maria Michela Cainazzo, Domenica Altavilla, Achille P. Caputi, Valeria Ghiaroni, Daniela Giuliani, Salvatore Guarini, Albertino Bigiani, Maria Passaniti, Alfio Bertolini, Carla Bazzani, Francesco Squadrito, Sheila Leone, Chiara Mioni |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2004 |
| Předmět: |
Atropine
Male medicine.medical_specialty Mean arterial pressure Physiology medicine.medical_treatment Electrophoretic Mobility Shift Assay Receptors Nicotinic Shock Hemorrhagic Acute hemorrhagic shock Chlorisondamine Vagus nerve chemistry.chemical_compound Adrenocorticotropin Physiology (medical) Internal medicine Hypovolemia Animals Medicine RNA Messenger Rats Wistar Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha business.industry NF-kappa B Vagus Nerve Vagotomy Rats Endocrinology Liver chemistry Acute Disease Cosyntropin Cholinergic Female I-kappa B Proteins Melanocortin medicine.symptom Cardiology and Cardiovascular Medicine business hormones hormone substitutes and hormone antagonists medicine.drug |
| Popis: | Objective : Several melanocortin peptides have a prompt and sustained resuscitating effect in conditions of hemorrhagic shock. The transcription nuclear factor kB (NF-kB) triggers a potentially lethal systemic inflammatory response, with marked production of tumor necrosis factor-α (TNF-α), 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) atabilized 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-kB activity and with decreased TNF-α mRNA liver content and TNF-α plasma levels. Bilateral cervical vagotomy, pretreatment with the melanocortin MC4 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-kB activity and TNF-α 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-kB-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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|