title: Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock.
abstract: We investigated whether electrical stimulation (STIM) of efferent vagus nerves may suppress nuclear factor (NF)-kappaB activation and the inflammatory cascade in hemorrhagic (Hem) shock.
  
  
  
  Rats were subjected to bilateral cervical vagotomy (VGX) or sham surgical procedures. Hem shock was induced by intermittent withdrawing of blood until mean arterial pressure stabilized within the range of 35 to 40 mm Hg. Application of constant voltage pulses to the caudal vagus ends (STIM; 5 V, 2 ms, 1 Hz for 12 minutes, 5 minutes after mean arterial pressure stabilization) increased survival time (VGX+Hem+Sham STIM=38+/-3 minutes; VGX+Hem+STIM >180 minutes), reverted the marked hypotension (VGX+Hem+Sham STIM=33+/-3 mm Hg; VGX+Hem+STIM=66+/-5 mm Hg), inhibited IkappaBalpha liver loss, and blunted the augmented NF-kappaB activity, decreased hepatic tumor necrosis factor (TNF)-alpha mRNA (VGX+Hem+Sham STIM=1.42+/-0.5 amount of TNF-alpha m-RNA; VGX+Hem+STIM=0.51+/-0.2 amount of TNF-alpha mRNA), and reduced plasma TNF-alpha (VGX+Hem+Sham STIM=190+/-24 pg/mL; VGX+Hem+STIM=87+/-15 pg/mL). Chlorisondamine, a nicotinic receptor antagonist, abated the effects of vagal stimulation.
  
  
  
  Our results show a parasympathetic inhibition of NF-kappaB by which the brain opposes NF-kappaB activation in the liver and modulates the inflammatory response during acute hypovolemic hemorrhagic shock.
authors.affiliation: Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Guarini
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Maria-Michela
authors.initials: MM
authors.lastname: Cainazzo
authors.forename: Daniela
authors.initials: D
authors.lastname: Giuliani
authors.forename: Albertino
authors.initials: A
authors.lastname: Bigiani
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Squadrito
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Alfio
authors.initials: A
authors.lastname: Bertolini
authors.forename: Rolando
authors.initials: R
authors.lastname: Marini
authors.forename: Elena B
authors.initials: EB
authors.lastname: Adamo
authors.forename: Francesco S
authors.initials: FS
authors.lastname: Venuti
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
mesh_terms: D000818:Animals; D001794:Blood Pressure; D004525:Efferent Pathways; D004558:Electric Stimulation; D020896:Hypovolemia / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000294:innervation / Q000378:metabolism; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009412:Nerve Fibers / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha