Role of prostacyclin in hemodynamic alterations in conscious rats with extrahepatic or intrahepatic portal hypertension.
Although prostaglandins are thought to be involved in the hyperdynamic circulation of portal hypertension, the role of this substance has not been elucidated. Dose-response curves, the hemodynamic effects of prostacyclin (20 micrograms/kg) and its inhibitor indomethacin and measurements of plasma and urinary levels of 6-keto-prostaglandin F1 alpha were compared in three groups of six rats each: normal, with portal vein stenosis and with secondary biliary cirrhosis. Plasma and urinary levels of 6-keto-prostaglandin F1 alpha were higher in rats with portal vein stenosis and cirrhotic rats than in normal rats. Dose-response curves showed similar maximal decreases in arterial pressure in the three groups, whereas the maximal increase in portal pressure was less marked in cirrhotic rats than in normal rats and rats with portal vein stenosis. In normal rats, prostacyclin increased cardiac output by 21% and portal pressure by 41%. Similar increases were observed in rats with portal vein stenosis. In contrast, prostacyclin did not affect cardiac output and portal pressure in cirrhotic rats. Indomethacin induced a more marked vasoconstrictive effect in normal rats than in cirrhotic rats. This study shows that prostacyclin plays a role in the hemodynamic alterations in portal hypertension. Moreover, the hyporeactivity observed in cirrhotic rats suggests that prostacyclin plays a major role in the circulatory changes of portal hypertension due to chronic liver disease.
Oberti
F
F
Laboratoire d'Hémodynamique Splanchnique, Unité de Recherches de Physiopathologie Hépatique (INSERM U-24), Hôpital Beaujon, Clichy, France.
Sogni
P
P
Cailmail
S
S
Moreau
R
R
Pipy
B
B
Lebrec
D
D
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood / Q000652:urine; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003135:Common Bile Duct / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006975:Hypertension, Portal / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply; D008105:Liver Cirrhosis, Biliary / Q000503:physiopathology*; D008297:Male; D011168:Portal System / Q000187:drug effects*; D011169:Portal Vein / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol; D007213:Indomethacin