• Yong-Hyuk Kim and Sun-Mee Lee.
• College of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu Suwon-si, Gyeonggi-do 440-746, Korea.
• Arch Pharm Res. 2004 Jan 1;27(1):111-7.

AbstractHepatic microcirculatory failure is a major component of reperfusion injury in the liver. Recent data provided some evidence that endothelium-derived vasoconstrictors and vasodilators may be functionally important to the control of the total hepatic blood flow under these conditions of circulatory failure. Since Kupffer cells provide signals that regulate the hepatic response in ischemia/reperfusion (I/R), the aim of this study was to investigate the role of Kupffer cells in the I/R-induced imbalance of vasoregulatory gene expression. Rats were subjected to 60 min hepatic ischemia, followed by 5 h of reperfusion. The Kupffer cells were inactivated by gadolinium chloride (GdCl3, 7.5 mg/kg body weight, intravenously) 1 day prior to ischemia. Liver samples were obtained 5 hrs after reperfusion for RT-PCR analysis of the mRNA for genes of interest: endothelin-1 (ET-1), its receptors ETA and ETB, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and heme oxygenase-1 (HO-1). ET-1 mRNA expression was increased by I/R. mRNA levels for ETA receptors showed no change, whereas ETB receptor transcripts increased in the I/R group. The increases in ET-1 and ETB mRNA were not prevented by the GdCl3 pretreatment. The mRNA levels for iNOS and eNOS significantly increased within the I/R group with no significant difference between the I/R group and the GdCl3-treated I/R group. HO-1 mRNA expression significantly increased in the I/R group and this increase was attenuated by GdCl3. In conclusion, we have demonstrated that an imbalance in hepatic vasoregulatory gene expression occurs during I/R. Our findings suggest that the activation of Kupffer cells is not required for I/R-induced hepatic microvascular dysfunction.

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