Document Detail


Leptin receptor blockade reduces intrahepatic vascular resistance and portal pressure in an experimental model of rat liver cirrhosis.
MedLine Citation:
PMID:  23886859     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increased hepatic vascular resistance mainly due to elevated vascular tone and to fibrosis is the primary factor in the development of portal hypertension in cirrhosis. Leptin, a hormone associated with reduction in nitric oxide bioavailability, vascular dysfunction and liver fibrosis, is increased in patients with cirrhosis. We aimed at evaluating whether leptin influences the increased hepatic resistance in portal hypertension. CCl4-cirrhotic rats received the leptin receptor-blocker ObR antibody, or its vehicle, every other day for 1 week. Hepatic and systemic hemodynamics were measured in both groups. Hepatic nitric oxide production and bioavalability, together with oxidative stress, nitrotyrosinated proteins, and liver fibrosis were evaluated. In cirrhotic rats, leptin-receptor blockade significantly reduced portal pressure without modifying portal blood flow, suggesting a reduction in the intrahepatic resistance. Portal pressure reduction was associated with increased nitric oxide bioavailability, and decreased O2- levels and nitrotyrosinated proteins. No changes in systemic hemodynamics and liver fibrosis were observed. Conclusion: The present study shows that blockade of the leptin signalling pathway in cirrhosis significantly reduces portal pressure. This effect is probably due to a nitric oxide-mediated reduction in the hepatic vascular tone.
Authors:
Maria Gabriela Delgado; Jordi Gracia-Sancho; Giusi Marrone; Aina Rodriguez-Vilarrupla; Ramon Deulofeu; Juan G Abraldes; Jaume Bosch; Juan Carlos Garcia-Pagan
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-25
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  -     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-26     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
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