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Erythropoietin improves skeletal muscle microcirculation in mice with sepsis through activation of eNOS
Author(s) -
Kao Raymond,
Xenocostas Anargyros,
Huang Weixiong,
Martin Claudio M.,
Rui Tao
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.752.3
Subject(s) - microcirculation , enos , sepsis , skeletal muscle , perfusion , erythropoietin , endocrinology , medicine , intravital microscopy , nitric oxide , nitric oxide synthase
This study is to explore the potential mechanisms involved in the improvement of microcirculation by the EPO in septic mice. Methods Sepsis was induced in mice by intraperitoneal injection of a fecal suspension (12.5 mg/mouse). The septic mice were given rHuEPO (400 U/kg) 18 hrs after sepsis. Capillary perfusion and nicotinamide adenine dinucleotide (NADH) fluorescence were observed using an intravital microscopy. In addition, endothelial cells derived from the skeletal muscle were treated with rHuEPO (5 U/ml) and eNOS activation and activity were assessed. Results Septic mice demonstrated microcirculatory dysfunction with a decreased capillary perfusion and an increased tissue NADH fluorescence indicating impaired tissue bioenergetics. In contrast, septic mice treated with rHuEPO resulted in an improvement in the perfused capillary density and decreased muscle NADH fluorescence. However, this beneficial effect of rHuEPO did not occur in septic mice treated with L‐NAME (20 mg/kg) or mice deficient in eNOS. Treatment of endothelial cells with rHuEPO resulted in an increase in eNOS phosphorylation and NO production. In conclusion Our results suggest that eNOS plays an important role in mediating the beneficial effect of rHuEPO on microcirculation in this model of sepsis. (Supported by funding from Department of National Defense, Canadian Forces Medical Group).