[Protective effect of the cholinergic anti-inflammatory pathway against hemorrhagic shock in rats].
OBJECTIVE
To investigate the effect of the cholinergic anti-inflammatory pathway on hemodynamics in hemorrhaged rats.


METHODS
Hemorrhagic shock was induced by modified Wiggers method until mean arterial pressure (MAP) was stabilized within the range of 35 to 40 mm Hg (1 mmHg=0.133 kPa). Thirty male Sprague-Dawley rats were randomly divided into six groups: sham group, hemorrhagic shock (Hem) group, vagotomy (VGX) group, vagus stimulation (STM) group, cholinergic inhibitor (THA) group and N receptor inhibitor (alpha-BGT) group. The distal end of the left vagus nerve trunk was placed on bipolar platinum electrode connected to a stimulation module and controlled by an acquisition system. Stimuli with constant voltage (5 V, 2 ms, 1 Hz) were applied to nerve for 12 minutes, starting 5 minutes after MAP stabilized at a level of 35 to 40 mmHg. Before stimulation a blood pressure transducer was implanted in the common carotid artery for continuous registration of MAP. Blood samples and liver samples were collected from animals of all groups after stimulation. Serum levels of tumor necrosis factor-alpha (TNF-alpha) and liver nuclear factor kappa-B (NF-KappaB) were determined.


RESULTS
MAP was markedly lowered at the end of bleeding, and the levels of serum TNF-alpha and liver NF-KappaB markedly increased 45 minutes after the bleeding was discontinued. Bilateral cervical vagotomy did not significantly modify the changes in serum TNF-alpha, but slightly increased liver NF-KappaB activation. Application of constant electric current to the distal end of the vagus trunk significantly reduced serum TNF-alpha and blunted liver NF-KappaB activation. Tetrahydroamino-acridine (THA,1.5 mg/kg, intravenous drip administration after bilateral cervical vagotomy reversed hypotension and attenuated serum TNF-alpha and liver NF-KappaB amounts, but alpha-bungarotoxin (1.0 microg/kg intravenous drip) pretreatment reverted the inhibitory effects of vagal stimulation.


CONCLUSIONS
The result suggest that direct electrical stimulation of the vagus nerve and its transmitter can significantly attenuate peak serum TNF-alpha amounts, inhibit the expression of liver NF-KappaB, and prevent the development of hypotension, thus it might produce a potential protective effect on hemorrhaged rats through acetylcholine (Ach) binds NAch receptor alpha 7 subunit which exists in the macrophage.
Li
Jian-guo
JG
Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei, China.
Hu
Zheng-fang
ZF
Du
Zhao-hui
ZH
Zhou
Qing
Q
Jia
Bao-hui
BH
Peng
Zhou-quan
ZQ
Ye
Xiao-feng
XF
Li
Bei
B
D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D006439:Hemodynamics; D008099:Liver / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D014630:Vagus Nerve
D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha