8-Isoprostaglandin F2 alpha, a product of lipid peroxidation, increases portal pressure in normal and cirrhotic rats.
OBJECTIVE
The F2-isoprostanes are a recently described class of prostaglandins formed by free radical-mediated lipid peroxidation. 8-Isoprostaglandin F2 alpha (8-iso-PGF2 alpha), an F2-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-PGF2 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-PGF2 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-PGF2 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.
Marley
R
R
Department of Academic Medicine, Royal Free Hospital School of Medicine, London, England.
Harry
D
D
Anand
R
R
Fernando
B
B
Davies
S
S
Moore
K
K
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D015227:Lipid Peroxidation; D008106:Liver Cirrhosis, Experimental / Q000503:physiopathology*; D008297:Male; D017082:Portal Pressure / Q000187:drug effects*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D019086:Bridged Bicyclo Compounds, Heterocyclic; D028441:F2-Isoprostanes; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011450:Prostaglandin Endoperoxides, Synthetic; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; D015237:Dinoprost