Endothelin-1 plays a major role in portal hypertension of biliary cirrhotic rats through endothelin receptor subtype B together with subtype A in vivo
| Autor: | Hideyuki Kojima, Hiroo Imazu, Shigeki Kuriyama, Masahito Uemura, Yoshihiro Nakatani, Jyunichi Yamao, Hitoshi Yoshiji, Hiroshi Fukui, Shinya Sakurai |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Endothelin Receptor Antagonists
Agonist medicine.medical_specialty Indoles medicine.drug_class Portal venous pressure Radioimmunoassay Gene Expression Blood Pressure Piperidines Internal medicine Hypertension Portal medicine Animals Protein Precursors Receptor Endothelin-1 Hepatology Liver Cirrhosis Biliary Receptors Endothelin Reverse Transcriptase Polymerase Chain Reaction business.industry Endothelins Hemodynamics Antagonist Azepines Receptor Endothelin A medicine.disease Receptor antagonist Receptor Endothelin B Endothelin 1 Rats Endocrinology Liver cardiovascular system RNA Portal hypertension Endothelin receptor business Oligopeptides |
| Zdroj: | Journal of Hepatology. 34:805-811 |
| ISSN: | 0168-8278 |
| DOI: | 10.1016/s0168-8278(01)00045-9 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect