Display Settings:

Format

Send to:

Choose Destination
We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Gastroenterology. 2000 Sep;119(3):794-805.

Hepatocyte-derived cysteinyl leukotrienes modulate vascular tone in experimental cirrhosis.

Author information

  • 1DNA Unit, Institut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.

Abstract

BACKGROUND & AIMS:

The leukotrienes C(4)/D(4)/E(4) (cysteinyl-LTs) are 5-lipoxygenase (5-LO)-derived eicosanoids with potent vasoconstrictor, proliferative, and profibrogenic properties that may participate in key pathophysiologic events in liver cirrhosis. We examined the cysteinyl-LT biosynthetic pathway in liver tissue and purified liver cells isolated from rats with carbon tetrachloride-induced cirrhosis, and assessed the vasoactive properties of LTD(4) in hepatic stellate cells (HSCs) and anesthetized rats.

METHODS & RESULTS:

Liver homogenates from cirrhotic rats had increased 5-LO mRNA and cysteinyl-LT content, as determined by Northern blot and enzyme immunoassay, respectively. In isolated rat liver cells, 5-LO mRNA expression was found to be restricted to Kupffer cells. However, among the liver cells (i.e., hepatocytes, Kupffer cells, HSCs, and sinusoidal endothelial cells), hepatocytes exhibited the highest ability to generate cysteinyl-LTs from the unstable intermediate LTA(4). Hepatocytes from cirrhotic rats showed an enhanced baseline generation of cysteinyl-LTs, but their ability to synthesize cysteinyl-LTs from exogenous LTA(4) was found to be similar to that of hepatocytes from normal animals. Both LTD(4) and hepatocyte-conditioned medium increased intracellular Ca(2+) concentration and induced contraction in HSCs, suggesting that hepatocyte-derived cysteinyl-LTs could act in a paracrine fashion on nearby nonparenchymal liver cells. The relevance of these in vitro findings was further established in vivo by the observation that LTD(4) significantly increased portal pressure in anesthetized rats.

CONCLUSIONS:

These data suggest a role for hepatocyte-derived cysteinyl-LTs in mediating hepatic vascular tone abnormalities in cirrhosis.

PMID:
10982774
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for Elsevier Science
    Loading ...
    Write to the Help Desk