8-ISOPROSTAGLANDIN F2-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 actin g via a thromboxane-like receptor. The aim of this study was to invest igate whether 8-iso-PGF(2 alpha) increases portal pressure. Methods: L ivers from normal and bile duct-ligated cirrhotic rats were perfused, and portal pressure response to infused agonist was monitored continuo usly. Results: Infusion of 8-iso-PGF(2 alpha) increased portal pressur e in both groups, with a significantly greater response in cirrhotic r ats, At a dose of 2.5 nmol/min, the mean portal pressure increased fro m 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. Th is response was completely blocked by SQ29548, a thromboxane receptor antagonist. A similar response pattern was observed with the thromboxa ne receptor agonist U46619. Conclusions: 8-iso-PGF(2 alpha) can increa se portal pressure in cirrhotic rats, If extrapolated to patients with cirrhosis, lipid peroxidation secondary to alcoholic liver injury, se psis, or other liver pathology may cause an acute increase in portal p ressure such as that observed in acute liver injury.