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Activated protein C restores hepatic microcirculation during sepsis by modulating vasoregulator expression.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2011 Oct; Vol. 36 (4), pp. 361-9. - Publication Year :
- 2011
-
Abstract
- Activated protein C (aPC) promotes fibrinolysis while inhibiting coagulation and inflammation. In septic patients, aPC levels are depleted, and aPC treatment has emerged as a therapeutic option. To better understand the mechanism(s) by which aPC improves survival in sepsis, we sought to determine the effect of aPC treatment on hepatic vasoactive gene and protein expression, leading to changes in hepatic vascular responsiveness in a septic animal model. Under anesthesia, rats underwent sham or cecal ligation and puncture followed by aPC treatment (1 mg/kg, twice daily, i.v.). Treatment with aPC significantly decreased hepatic endothelin 1 (ET-1)/ET A receptor mRNA and protein expression. To determine the effect of aPC on hepatic microvasculature, ET-1-induced changes in liver microcirculation were assessed by intravital microscopy. This approach demonstrated aPC significantly improved hepatic perfusion index in the animals that underwent cecal ligation and puncture in the absence of significant changes in portal venous pressure. Furthermore, although aPC did not affect ET-1-dependent sinusoidal vasoconstriction, aPC induced hepatoprotective effects via enhanced red blood cell velocity. Collectively, these data demonstrate aPC ameliorates ET-1-dependent changes in hepatic microcirculation and improves hepatic function in the setting of sepsis.
- Subjects :
- Animals
Endothelin-1 genetics
Endothelin-1 metabolism
Male
Random Allocation
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A genetics
Receptor, Endothelin A metabolism
Sepsis drug therapy
Sepsis metabolism
Liver drug effects
Liver metabolism
Microcirculation drug effects
Protein C therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 36
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 21897335
- Full Text :
- https://doi.org/10.1097/SHK.0b013e31822c7380