HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/4/G763    most recent 00300.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Graupera, M. Articles by García-Pagán, J.-C. Search for Related Content PubMed PubMed Citation Articles by Graupera, M. Articles by García-Pagán, J.-C.

LIVER AND BILIARY TRACT

Sinusoidal endothelial COX-1-derived prostanoids modulate the hepatic vascular tone of cirrhotic rat livers

¹Hepatic Hemodynamic Laboratory, Liver Unit, Institut Malalties Digestives, Hospital Clínic and ²Immunology Unit, Department of Cellular Biology and Pathology, Institut d’Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain

Submitted 8 July 2004 ; accepted in final form 13 November 2004

CCl₄ cirrhotic rat liver exhibits a hyperresponse to the ₁-adrenergic agonist methoxamine (Mtx) that is associated with enhanced thromboxane A₂ (TXA₂) production and is abrogated by indomethacin. To further elucidate the molecular mechanisms involved in the hyperresponse to vasoconstrictors, portal perfusion pressure dose-response curves to Mtx were performed in CCl₄ cirrhotic rats livers after preincubation with vehicle, the cyclooxygenase (COX)-1 selective inhibitor SC-560, and the COX-2 selective inhibitor SC-236. TXA₂ production was determined in samples of the perfusate. COX-1 expression was analyzed and quantified in hepatocytes, Kupffer cells, sinusoidal endothelial cells (SEC), and hepatic stellate cells (HSC) isolated from control and cirrhotic rat livers by double-immunofluorescence staining, with specific markers for each population using flow cytometry or Western blot analysis. COX-1 protein levels were not significantly increased in cirrhotic livers, but COX-2 protein expression was increased. COX-1 inhibition, but not COX-2, significantly attenuated the response to Mtx and prevented the increased production of TXA₂. Cirrhotic livers showed an increased expression of COX-1 in SEC and reduced expression in HSC compared with control livers, whereas COX-1 was similarly distributed in Kupffer cells. Despite abundant hepatic COX-2 expression, the increased response to Mtx of cirrhotic livers is mainly dependent of COX-1. Upregulation of COX-1 in cirrhotic SEC may be responsible for the hyperesponse to Mtx.

portal pressure; hepatic cyclooxygenase expression; selective cyclooxygenase inhibition; nonparenchymal cells

This article has been cited by other articles:

				B. Vollmar and M. D. Menger The Hepatic Microcirculation: Mechanistic Contributions and Therapeutic Targets in Liver Injury and Repair Physiol Rev, October 1, 2009; 89(4): 1269 - 1339. [Abstract] [Full Text] [PDF]