Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock.
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.
Guarini
Salvatore
S
Department of Biomedical Sciences, Section of Pharmacology, University of Modena and Reggio Emilia, Modena, Italy.
Altavilla
Domenica
D
Cainazzo
Maria-Michela
MM
Giuliani
Daniela
D
Bigiani
Albertino
A
Marini
Herbert
H
Squadrito
Giovanni
G
Minutoli
Letteria
L
Bertolini
Alfio
A
Marini
Rolando
R
Adamo
Elena B
EB
Venuti
Francesco S
FS
Squadrito
Francesco
F
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*
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