title: Increased EETs participate in peripheral endothelial dysfunction of cirrhosis.
abstract: The hyperdynamic circulation of cirrhosis participates in the pathophysiology of portal hypertension. P450-dependent epoxyeicosatrienoic acids (EET) are potent vasodilators. We evaluated plasma levels of EETs in cirrhotic patients and the effect of epoxygenase and nitric oxide synthase (NOS) inhibition on skin blood flow, measured by laser Doppler flowmetry, in normal subjects and cirrhotic patients with and without ascites. Free plasma EETs were increased in cirrhotic patients compared to normal subjects, while the ratio between 8,9-, 11,12-, and 14-15-EET was the same. In cirrhotic patients without ascites, skin blood flow was significantly increased compared to normal subjects. In patients with ascites skin blood flow was significantly reduced compared to control subjects and patients without ascites. Inhibition of epoxygenase with miconazole and of NOS with L-NG-Nitroarginine methyl ester (L-NAME) decreased basal skin flow in normal subjects and in cirrhotic patients, the effect being higher in cirrhotic patients. Miconazole caused a further decrease in flow when administered with L-NAME, both in normal subjects and in cirrhotic patients. In conclusion, EETs participate in the control of peripheral circulation of normal subjects and in the pathophysiology of peripheral vasodilatation of cirrhotic patients with ascites.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Padova, Via Giustiniani 2, 35100 Padova, Italy. david.sacerdoti@unipd.it
authors.forename: David
authors.initials: D
authors.lastname: Sacerdoti
authors.forename: Despina
authors.initials: D
authors.lastname: Mania
authors.forename: Houli
authors.initials: H
authors.lastname: Jiang
authors.forename: Paola
authors.initials: P
authors.lastname: Pesce
authors.forename: Silvia
authors.initials: S
authors.lastname: Gaiani
authors.forename: Angelo
authors.initials: A
authors.lastname: Gatta
authors.forename: Massimo
authors.initials: M
authors.lastname: Bolognesi
mesh_terms: D015777:Eicosanoids / Q000097:blood*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000503:physiopathology*; D008297:Male; D008825:Miconazole / Q000494:pharmacology; D008875:Middle Aged; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010105:Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects
chemical_list: D015777:Eicosanoids; D008825:Miconazole; D010105:Oxygenases; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester