title: Effect of endothelin A receptor antagonist on hepatic hemodynamics in cirrhotic rats. Implications for endothelin-1 in portal hypertension.
abstract: OBJECTIVE
  The effect of an endothelin (ET) A receptor antagonist on hepatic hemodynamics in cirrhotic rats was examined.
  
  
  METHODS
  Portal pressure and hepatic tissue blood flow in cirrhotic rats were measured. Plasma ET-1 levels were determined by radioimmunoassay. BQ-123 was infused to these rats at a rate of 10 nmol/min. The sinusoids were observed by scanning electron microscopy. The localization of ET-1 and ETA receptors was examined using the indirect immunoperoxidase method.
  
  
  RESULTS
  In cirrhotic rats, the portal pressure significantly increased to 16.6 ± 1.5 cm H2O, and the hepatic tissue blood flow markedly decreased. Plasma ET-1 levels in cirrhotic rats were higher than those in normal rats. When BQ-123 was infused, the portal pressure was significantly reduced by more than 2 cm H2O, compared with the control group (p < 0.05). Hepatic tissue blood flow was maintained at the level before infusion. In liver cirrhosis, the sinusoids were covered with continuous endothelial cells, and the number of sinusoidal endothelial fenestrae extremely decreased. ET-1 was remarkably enhanced in sinusoidal endothelial cells within the regenerating nodules, and the reaction products of ETA receptors were mainly recognized in hepatic stellate cells.
  
  
  CONCLUSIONS
  The augmented action of ET-1 via the ETA receptor may be involved in the mechanism of portal hypertension in liver cirrhosis.
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Tokai University School of Medicine, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Takashimizu
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Kojima
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishizaki
authors.forename: Tatehiro
authors.initials: T
authors.lastname: Kagawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Shiraishi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mine
authors.forename: Norihito
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D042783:Endothelial Cells / Q000187:drug effects / Q000648:ultrastructure; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000648:ultrastructure; D006975:Hypertension, Portal / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000648:ultrastructure; D008102:Liver Circulation / Q000187:drug effects*; D008106:Liver Cirrhosis, Experimental / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)