The effect of endothelin and its antagonist Bosentan on hemodynamics and microvascular exchange in cirrhotic rat liver

Background/Aims: To characterize the effects of endothelin-1 and of Bosentan, a mixed endothelin antagonist, on hepatic hemodynamics in cirrhotic animals in vivo and on hepatic microvascular exchange in the perfused rat liver. Methods: Biliary cirrhosis was induced by bile duct ligation, and microno...

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Bibliographic Details
Published in:Journal of hepatology 1998-06, Vol.28 (6), p.1020-1030
Main Authors: Reichen, Jürg, Gerbes, Alexander L., Steiner, MArkus J., Sägesser, Hans, Clozel, Martine
Format: Article
Language:English
Subjects:
Animals
Bile Acids and Salts - blood
Bile Ducts - physiology
Bilirubin - blood
Biological and medical sciences
Blood Pressure - drug effects
Body Weight - drug effects
Bosentan
Carbon Tetrachloride Poisoning
Cardiac Output - drug effects
Cirrhosis
Digestive system
Endothelin-1 - pharmacokinetics
Endothelin-1 - pharmacology
Endothelin-1 - physiology
Hemodynamics - drug effects
Hemodynamics - physiology
Hepatic Artery - drug effects
Hepatic Artery - physiology
Hepatic Artery - physiopathology
Liver - blood supply
Liver Circulation - drug effects
Liver Circulation - physiology
Liver Cirrhosis, Biliary - blood
Liver Cirrhosis, Biliary - chemically induced
Liver Cirrhosis, Biliary - physiopathology
Male
Medical sciences
Metabolic Clearance Rate
Microcirculation - drug effects
Microcirculation - physiology
Microspheres
Multiple indicator dilution technique
Organ Size - drug effects
Perfused liver
Pharmacology. Drug treatments
Phenobarbital
Plasma endothelin
Portal blood flow
Portal hypertension
Portal pressure
Portal System - drug effects
Rats
Rats, Sprague-Dawley
Sulfonamides - pharmacology
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Summary:Background/Aims: To characterize the effects of endothelin-1 and of Bosentan, a mixed endothelin antagonist, on hepatic hemodynamics in cirrhotic animals in vivo and on hepatic microvascular exchange in the perfused rat liver. Methods: Biliary cirrhosis was induced by bile duct ligation, and micronodular cirrhosis by chronic exposure to phenobarbital/CCl 4 in male rats. Hepatic hemodynamics were studied under basal conditions and after administration of Bosentan (3–30 mg/kg) by the microsphere technique. Microvascular exchange was assessed in the in situ perfused rat liver by the multiple indicator dilution technique. Results: Bosentan lowered portal pressure in a dose-dependent fashion; at the highest dose tested, this decrease averaged −29±11 and −26±8% in biliary and micronodular cirrhosis, respectively ( p
ISSN:0168-8278
1600-0641
DOI:10.1016/S0168-8278(98)80352-8