Mixed endothelin receptor antagonist, SB209670, decreases portal pressure in biliary cirrhotic rats in vivo by reducing portal venous system resistance
| Autor: | Masahito Uemura, Hideyuki Kojima, Jyunichi Yamao, Tatsuhiro Tsujimoto, Hiroshi Fukui, Akira Takaya |
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| Rok vydání: | 2000 |
| Předmět: |
Endothelin Receptor Antagonists
Male medicine.medical_specialty Radioactive microsphere technique Portal venous pressure Portal venous system Liver Cirrhosis Experimental Renal Circulation Rats Sprague-Dawley Internal medicine medicine Animals Hepatology Endothelin-1 Endothelin receptor antagonist business.industry Portal Vein Arteries medicine.disease Portal Pressure Rats Blood pressure Endocrinology Liver Renal blood flow Indans Portal hypertension Vascular Resistance Endothelin receptor business |
| Zdroj: | Journal of hepatology. 32(1) |
| ISSN: | 0168-8278 |
| Popis: | This study aimed to evaluate the hemodynamic effects of endothelin-1 or mixed endothelin receptor antagonist, SB209670 in cirrhotic rats, and to elucidate the role of endothelin in cirrhotic portal hypertension.Secondary biliary cirrhosis was induced by bile duct ligation. Hemodynamics were studied using the radioactive microsphere technique.Plasma and hepatic endothelin levels in cirrhotic rats were significantly higher than those in normal rats (plasma, 9.0+/-1.3 vs. 2.6+/-0.5 pg/ml, p0.001; liver, 74.8+/-13.3 vs. 12.6+/-2.5 pg/g wet tissue, p0.001). Intraportal administration of endothelin-1 (3 nmol/kg) progressively raised portal pressure without an initial transient reduction, which was observed in systemic arterial pressure, in both cirrhotic and normal rats. SB209670 (5.4 micromol/kg) reduced portal pressure in cirrhotic rats (-19+/-5%, p0.01) without modifying systemic arterial pressure and renal blood flow, but not in normal rats. This reduction was associated with reduced portal venous system resistance (vehicle, 2.5+/-0.2 vs. SB209670, 1.7+/-0.1 mmHg x min x 100 g bw/ml, p0.01), but not with change in portal venous inflow and collateral blood flow.Mixed endothelin antagonist, SB209670, decreased portal pressure by reducing portal venous system resistance without modifying systemic arterial pressure and renal blood flow in cirrhotic rats. This result, together with the findings that plasma and hepatic endothelin levels were elevated in cirrhotic rats and that exogenous endothelin-1 increased portal pressure, provides further support for a role of endothelin in portal hypertension and suggests a potential use of mixed endothelin antagonist in the pharmacological treatment of portal hypertension. |
| Databáze: | OpenAIRE |
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