Inhibition of complement C3 might rescue vascular hyporeactivity in a conscious hemorrhagic shock rat model.
Microvasc Res
; 105: 23-9, 2016 May.
Article
in En
| MEDLINE
| ID: mdl-26687560
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Shock, Hemorrhagic
/
Vasoconstriction
/
Vasoconstrictor Agents
/
Complement C3
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Receptors, Complement 3b
/
Mesenteric Artery, Superior
/
Complement Activation
/
Elapid Venoms
/
Complement Inactivating Agents
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Microvasc Res
Year:
2016
Document type:
Article