Inhibition of complement C3 might rescue vascular hyporeactivity in a conscious hemorrhagic shock rat model.

Abstract:

BACKGROUND:Vascular hyporeactivity in severe hemorrhagic shock could induce refractory hypotension and is an important cause of death. The global acute inflammatory response induced in shock triggers the over-expression of reactive oxygen species, NO, ET1 and TNF-α, which play essential roles in the pathology of vascular hyporeactivity. This leads to a hypothesis that inhibition of the complement system, the mediator of the inflammatory cascade, might be a promising therapeutic exploration for vascular hyporeactivity. METHODS:We use cobra venom factor (CVF) and the soluble form of CR1 (sCR1) which deplete or inhibit complement C3 respectively to examine its role in vascular hyporeactivity in a conscious hemorrhagic shock rat model. RESULTS:We first confirmed the over-activation of C3 during shock and the down-regulation effects of CVF and sCR1 on C3. Then, both CVF and sCR1 could significantly mitigate the over-expression of serum NO, ET-1, TNF-α and reactive oxygen species. Finally, the vascular reactivity of superior mesenteric arteries (SMA) was examined in vitro, which confirmed the massive reduction of vascular reactivity in shock, which was significantly rescued by both CVF and sCR1. CONCLUSIONS:Inhibition of C3 might improve the reactivity of SMA to norepinephrine during hemorrhagic shock possibly through the downregulation of NO, ET1, TNF-α and reactive oxygen radicals.

journal_name

Microvasc Res

journal_title

Microvascular research

authors

Chen D,Song MQ,Liu YJ,Xue YK,Cheng P,Zheng H,Chen LB

doi

10.1016/j.mvr.2015.12.006

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

23-9

eissn

0026-2862

issn

1095-9319

pii

S0026-2862(15)30044-3

journal_volume

105

pub_type

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