Efferent vagal fibre stimulation blunts nuclear factor-kappaB activation and protects against hypovolemic hemorrhagic shock.

Abstract:

BACKGROUND: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. METHODS AND RESULTS: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. CONCLUSIONS: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.

journal_name

Circulation

journal_title

Circulation

authors

Guarini S,Altavilla D,Cainazzo MM,Giuliani D,Bigiani A,Marini H,Squadrito G,Minutoli L,Bertolini A,Marini R,Adamo EB,Venuti FS,Squadrito F

doi

10.1161/01.cir.0000050627.90734.ed

subject

Has Abstract

pub_date

2003-03-04 00:00:00

pages

1189-94

issue

8

eissn

0009-7322

issn

1524-4539

journal_volume

107

pub_type

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