| Enhanced vasoconstrictor prostanoid production by sinusoidal endothelial cells increases portal perfusion pressure in cirrhotic rat livers. | |
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MedLine Citation:
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PMID: 17459512 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Cyclooxygenase-1 (COX-1) is overexpressed in sinusoidal endothelial cells (SEC) of cirrhotic rat livers, and through an enhanced production of vasoconstrictor prostanoids contributes to increase intrahepatic resistance. Our study was aimed at investigating the role of enhanced AA bioavailability modulating the hepatic vascular tone of cirrhotic livers and identifying which prostanoid is involved. METHODS: SEC isolated from control and cirrhotic rat livers were incubated with AA, methoxamine or vehicle. TXA(2) was quantified. In addition, portal perfusion pressure (PP) response curves to AA were performed in rat livers pre-incubated with vehicle, SC-560 (COX-1 inhibitor), Furegrelate (inhibitor of TXA(2) synthesis) and SQ-29548 (PGH(2)/TXA(2) receptor blocker). cPLA2 activity was determined in control and cirrhotic livers. RESULTS: AA and methoxamine incubation promoted a significant increase in TXA(2) release by Cirrhotic-SEC, but not in Control-SEC. AA produced a dose-dependent increase in the PP, associated with increased TXA(2) release. These responses were significantly greater in cirrhotic livers. COX-1 inhibition and PGH(2)/TXA(2) receptor blockade, but not TXA(2) synthase inhibition, markedly attenuated the PP response to AA of cirrhotic livers. Additionally, cirrhotic livers exhibited significantly increased cPLA2 activity. CONCLUSIONS: An enhanced production of vasoconstrictor prostanoids, probably PGH(2), by SEC contributes to increase vascular tone of cirrhotic livers. |
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Authors:
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Jorge Gracia-Sancho; Bàrbara Laviña; Aina Rodríguez-Vilarrupla; Héctor García-Calderó; Jaime Bosch; Joan Carles García-Pagán |
Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't Date: 2007-04-05 |
Journal Detail:
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Title: Journal of hepatology Volume: 47 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2007 Aug |
Date Detail:
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Created Date: 2007-07-10 Completed Date: 2007-10-18 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 220-7 Citation Subset: IM |
Affiliation:
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Hepatic Hemodynamic Laboratory, Liver Unit, IMDIM, Hospital Clínic, Ciberehd and Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Villarroel 170, 08036 Barcelona, Spain. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / administration & dosage, pharmacokinetics, pharmacology Biological Availability Cyclooxygenase 1 / drug effects Cyclooxygenase Inhibitors / pharmacology Dose-Response Relationship, Drug Endothelial Cells / metabolism* Enzyme Inhibitors / pharmacology Liver / blood supply* Liver Cirrhosis / physiopathology* Male Perfusion Phospholipases A / metabolism Portal System / drug effects, physiopathology* Pressure Prostaglandins / biosynthesis* Rats Rats, Wistar Receptors, Thromboxane A2, Prostaglandin H2 / antagonists & inhibitors Thromboxane B2 / biosynthesis Thromboxane-A Synthase / antagonists & inhibitors Vasoconstriction Vasoconstrictor Agents / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Cyclooxygenase Inhibitors; 0/Enzyme Inhibitors; 0/Prostaglandins; 0/Receptors, Thromboxane A2, Prostaglandin H2; 0/Vasoconstrictor Agents; 506-32-1/Arachidonic Acid; 54397-85-2/Thromboxane B2; EC 1.14.99.1/Cyclooxygenase 1; EC 3.1.1.-/Phospholipases A; EC 5.3.99.5/Thromboxane-A Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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