Altered expression of endothelin, vascular endothelial growth factor, and its receptor in hepatic tissue in endotoxemic rat.
Sepsis involves a heterogeneous class of syndromes, and septic shock, a severe form of sepsis, is associated with the development of progressive damage in multiple organs. The present study examined the time-dependent alterations of endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) levels in liver tissue in a septic rat model. Healthy male Wistar rats aged 15 weeks received 15 mg/kg lipopolysaccharide (LPS) and were sacrificed at different time points (1, 3, 6, and 10 hrs after treatment). Rats that did not receive LPS were considered to be controls. A 28-fold increase in the ET-1 level was observed in liver tissue 10 hrs after LPS administration. VEGF was also altered in hepatic tissue in a time-dependent manner. A gradual increase of VEGF expression in liver tissue after LPS administration was observed. Expression of Flt-1, the vascular permeability receptor of VEGF, was also increased in liver tissue after LPS administration. ET-1 is a potent vasoconstrictor and, therefore, may play a role in the regulation of hepatic perfusion in a sepsis model. On the other hand, VEGF may be involved in capillary leakage in liver tissue after LPS administration. The present findings suggest that there might be a loss of balance between the ET-1 and VEGF levels in the septic liver at different time points, which could contribute to the pathogenesis of acute liver injury in endotoxemia.
Zaedi
Sohel
S
Department of Cardiovascular Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.
Jesmin
Subrina
S
Yamaguchi
Naoto
N
Shimojo
Nobutake
N
Maeda
Seiji
S
Gando
Satoshi
S
Yamaguchi
Iwao
I
Goto
Katsutoshi
K
Miyauchi
Takashi
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000032:analysis / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D020556:Neutrophil Infiltration; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000097:blood / Q000235:genetics / Q000378:metabolism*
D019332:Endothelin-1; D008070:Lipopolysaccharides; D042461:Vascular Endothelial Growth Factor A