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INFECTION

Altered Expression of Endothelin, Vascular Endothelial Growth Factor, and Its Receptor in Hepatic Tissue in Endotoxemic Rat

Sohel Zaedi^*, Subrina Jesmin^*, Naoto Yamaguchi^*, Nobutake Shimojo^*, Seiji Maeda^*, Satoshi Gando, Iwao Yamaguchi^*, Katsutoshi Goto and Takashi Miyauchi^*,1

^* Department of Cardiovascular Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki 305-8575, Japan; Department of Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan; and Department of Pharmacology, Institute of Basic Science, University of Tsukuba, Ibaraki 305-8575, Japan

To whom requests for reprints should be addressed at ¹ Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan. E-mail: t-miyauc{at}md.tsukuba.ac.jp

Abstract

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.

Key Words: LPS • sepsis • liver • endothelin • VEGF