Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo

J Hepatol. 2001 Jun;34(6):805-11. doi: 10.1016/s0168-8278(01)00045-9.


Background/aims: Endothelin-1 has been suggested to play a key role in cirrhotic portal hypertension, but a role of its receptors in vivo is not fully elucidated.

Methods: Biliary cirrhosis was induced by bile duct ligation. Expressions of endothelin-1 and its receptors were evaluated by radioimmunoassay and/or reverse-transcription polymerase chain reaction. Hemodynamics were studied using endothelin receptor agonist or antagonist.

Results: Portal pressure and hepatic endothelin-1 concentrations progressively increased in parallel after bile duct ligation. Gene expression of hepatic prepro-endothelin-1 and endothelin B receptor enhanced after bile duct ligation, while that of endothelin A receptor was unchanged. Intraportal administration of endothelin-1 or endothelin B receptor agonist sarafotoxin 6c (0.5 nmol/kg, respectively) progressively raised portal pressure in both sham and cirrhotic rats. Portal hypertensive effect of sarafotoxin 6c was more intense in cirrhotic rats than sham animals. Neither endothelin A receptor antagonist FR139317 (1 mg/kg) nor endothelin B receptor antagonist BQ788 (1 mg/kg) alone ameliorated cirrhotic portal hypertension. Only the combined endothelin A and B blockade was associated with a decrease in portal pressure in cirrhotic rats.

Conclusions: These results indicate that endothelin-1 plays a major role in cirrhotic portal hypertension through endothelin receptor subtype B together with subtype A in vivo.

MeSH terms

  • Animals
  • Azepines / pharmacology
  • Blood Pressure
  • Endothelin Receptor Antagonists
  • Endothelin-1 / genetics
  • Endothelin-1 / physiology*
  • Endothelins / genetics
  • Gene Expression
  • Hemodynamics
  • Hypertension, Portal / etiology*
  • Hypertension, Portal / genetics
  • Hypertension, Portal / physiopathology
  • Indoles / pharmacology
  • Liver / physiopathology
  • Liver Cirrhosis, Biliary / complications*
  • Liver Cirrhosis, Biliary / genetics
  • Liver Cirrhosis, Biliary / physiopathology
  • Oligopeptides / pharmacology
  • Piperidines / pharmacology
  • Protein Precursors / genetics
  • RNA / genetics
  • Radioimmunoassay
  • Rats
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin / genetics
  • Receptors, Endothelin / physiology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Azepines
  • Endothelin Receptor Antagonists
  • Endothelin-1
  • Endothelins
  • Indoles
  • Oligopeptides
  • Piperidines
  • Protein Precursors
  • Receptor, Endothelin A
  • Receptor, Endothelin B
  • Receptors, Endothelin
  • FR 139317
  • BQ 788
  • RNA