Document Detail

Role of thromboxane A2 in early BDL-induced portal hypertension.
MedLine Citation:
PMID:  12431905     Owner:  NLM     Status:  MEDLINE    
Although the mechanisms of cirrhosis-induced portal hypertension have been studied extensively, the role of thromboxane A(2) (TXA(2)) in the development of portal hypertension has never been explicitly explored. In the present study, we sought to determine the role of TXA(2) in bile duct ligation (BDL)-induced portal hypertension in Sprague-Dawley rats. After 1 wk of BDL or sham operation, the liver was isolated and perfused with Krebs-Henseleit bicarbonate buffer at a constant flow rate. After 30 min of nonrecirculating perfusion, the buffer was recirculated in a total volume of 100 ml. The perfusate was sampled for the enzyme immunoassay of thromboxane B(2) (TXB(2)), the stable metabolite of TXA(2). Although recirculation of the buffer caused no significant change in sham-operated rats, it resulted in a marked increase in portal pressure in BDL rats. The increase in portal pressure was found concomitantly with a significant increase of TXB(2) in the perfusate (sham vs. BDL after 30 min of recirculating perfusion: 1,420 +/- 803 vs. 10,210 +/- 2,950 pg/ml; P < 0.05). Perfusion with a buffer containing indomethacin or gadolinium chloride for inhibition of cyclooxygenase (COX) or Kupffer cells, respectively, substantially blocked the recirculation-induced increases in both portal pressure and TXB(2) release in BDL group. Hepatic detection of COX gene expression by RT-PCR revealed that COX-2 but not COX-1 was upregulated following BDL, and this upregulation was confirmed at the protein level by Western blot analysis. In conclusion, these results clearly demonstrate that increased hepatic TXA(2) release into the portal circulation contributes to the increased portal resistance in BDL-induced liver injury, suggesting a role of TXA(2) in liver fibrosis-induced portal hypertension. Furthermore, the Kupffer cell is likely the source of increased TXA(2), which is associated with upregulation of the COX-2 enzyme.
Yukihiro Yokoyama; Hongzhi Xu; Nicole Kresge; Steve Keller; Amir H Sarmadi; Rajiv Baveja; Mark G Clemens; Jian X Zhang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2002-11-13
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  284     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-10     Completed Date:  2003-03-10     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G453-60     Citation Subset:  IM    
Department of Biology, University of North Carolina at Charlotte, 9201 University City Boulevard, Charlotte, NC 28223, USA.
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MeSH Terms
Alanine Transaminase / metabolism
Bile Ducts / physiology*
Blood Pressure / physiology
Blotting, Western
Cyclooxygenase 2
Hypertension, Portal / pathology,  physiopathology*
Isoenzymes / biosynthesis
Kupffer Cells / pathology
L-Lactate Dehydrogenase / metabolism
Liver / enzymology,  metabolism,  pathology
Portal Vein / physiology
Prostaglandin-Endoperoxide Synthases / biosynthesis,  physiology
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Thromboxane A2 / physiology*
Thromboxane B2 / biosynthesis,  genetics
Up-Regulation / drug effects
Grant Support
Reg. No./Substance:
0/Isoenzymes; 54397-85-2/Thromboxane B2; 57576-52-0/Thromboxane A2; EC Dehydrogenase; EC 2; EC Synthases; EC Transaminase

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