Possible protection of sinusoidal endothelial cells by endothelin B receptor during hepatic warm ischemia-reperfusion.
OBJECTIVE
Endothelins (ETs) are important regulators of the hepatic microcirculation. We investigated the pure biological roles of endothelin B receptors (ETB-Rs) on hepatic warm ischemia-reperfusion (I/R) injury using ETB-R deficient spotting lethal (sl) rats.


METHODS
Homozygous (sl/sl) and wild-type (+/+) rats were exposed to 60 min of 92% partial hepatic ischemia and then were killed at 2, 6, and 24 h, and 3 and 7 days after reperfusion. We measured the serum alanine aminotransferase (ALT) levels to assess hepatocyte injury, and the serum hyaluronic acid (HA) levels and factor VIII-related antigen (FVIIIRAg) staining to assess sinusoidal endothelial cell (SEC) injury. We also measured the concentrations of ET-1 and nitrite (NO2-) and nitrate (NO3-) of liver tissue samples.


RESULTS
Although no significant difference was observed in the ALT levels, the HA levels were significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding FVIIIRAg staining, positive SECs were enhanced in the sl/sl rats. The ET-1 levels were also significantly elevated at an early stage after reperfusion in the sl/sl rats. Regarding the NO2- and NO3- levels, no significant difference was observed.


CONCLUSIONS
Endothelin B receptor was shown to have a protective effect on SECs through the inhibition of ET-1 during hepatic warm I/R injury.
Mochizuki
Kyoko
K
Department of Transplantation and Digestive Surgery, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, Nagasaki, 852-8501, Japan.
Ohno
Yasuharu
Y
Kanematsu
Takashi
T
Sakurai-Yamashita
Yasuko
Y
Niwa
Masami
M
Hishikawa
Yoshitaka
Y
Koji
Takehiko
T
D000818:Animals; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism*; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008833:Microcirculation / Q000503:physiopathology; D051381:Rats; D044023:Receptor, Endothelin B / Q000502:physiology*; D015427:Reperfusion Injury / Q000209:etiology / Q000503:physiopathology*; D052096:Warm Ischemia / Q000009:adverse effects
D019332:Endothelin-1; D044023:Receptor, Endothelin B