8-isoprostaglandin F-2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats

Background & Aims: The F-2-isoprostanes are a recently described class of prostaglandins formed by free radical-mediated lipid peroxidation. 8-Isoprostaglandin F-2 alpha (8-iso-PGF(2 alpha)), an F-2-isoprostane, has previously been shown to be a potent renal vasoconstrictor acting via a thromboxane-like receptor. The aim of this study was to investigate whether 8-iso-PGF(2 alpha) increases portal pressure. Methods: Livers from normal and bile duct-ligated cirrhotic rats were perfused, and portal pressure response to infused agonist was monitored continuously. Results: Infusion of 8-iso-PGF(2 alpha) increased portal pressure in both groups, with a significantly greater response in cirrhotic rats, At a dose of 2.5 nmol/min, the mean portal pressure increased from a baseline of 8.2 +/- 0.6 to 9.8 +/- 1.3 mm Hg, whereas in cirrhotic animals, the increase was from 12.0 +/- 0.9 to 18.6 +/- 1.8 mm Hg. This response was completely blocked by SQ29548, a thromboxane receptor antagonist. A similar response pattern was observed with the thromboxane receptor agonist U46619. Conclusions: 8-iso-PGF(2 alpha) can increase portal pressure in cirrhotic rats, If extrapolated to patients with cirrhosis, lipid peroxidation secondary to alcoholic liver injury, sepsis, or other liver pathology may cause an acute increase in portal pressure such as that observed in acute liver injury.