Document Detail

Non-alcoholic steatohepatitis induces non-fibrosis-related portal hypertension associated with splanchnic vasodilation and signs of a hyperdynamic circulation in vitro and in vivo in a rat model.
MedLine Citation:
PMID:  19840249     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Steatosis, without fibrosis, may lead to changes in liver blood flow, which are poorly understood, and to date have not been correlated to portal pressure and related haemodynamics. AIMS: To study the temporal relation between progressive steatosis, portal pressure, systemic haemodynamics, vascular responsiveness, mesenteric and portal blood flow in methionine-choline-deficient diet (MCDD)-fed rats. METHODS: Male Wistar rats fed the MCDD were examined at week (w) 0-1-2-3-4-5-6-7-8, respectively, including systemic haemodynamics and portal pressure. At w0-4-8, in vivo blood flow was measured in the portal vein and the superior mesenteric artery. Dose-response curves to phenylephrine (PE) were established in abdominal aortic rings. RESULTS: Histology showed 100% steatosis from w3 on. Fibrosis was absent. Significant inflammation was nearly absent upon w4. Portal pressure slightly increased at w2, reached a maximum at w4 [9.4 +/- 0.3 vs 2.9 +/- 0.6 mmHg at w0 (P=0.003)] and remained stable upon w8. Mean arterial blood pressure (MABP) decreased from w2 on [98.7 +/- 5.7 mmHg on w4 compared with 123.8 +/- 1.8 on w0 (P=0.002)]. Portal flow increased from 1.85 +/- 0.11 to 3.07 +/- 0.44 ml/min/100 g on w0 and w8 respectively (P=0.039). Mesenteric artery flow increased from 3.40 +/- 0.26 to 4.56 +/- 0.30 ml/min/100 g on w0 and w8 respectively (P=0.043). Vascular responsiveness to PE gradually decreased from 138 +/- 3% on w0 to 110 +/- 5% on w4 (P=0.013). CONCLUSION: Steatohepatitis induces significant portal hypertension (PHT) in the absence of fibrosis, associated with an increase in mesenteric arterial and portal venous flow, arterial hyporesponsiveness to vasoconstrictors and a decrease in MABP, indicating the presence of splanchnic vasodilation and hyperdynamic circulation. These alterations resemble those seen in cirrhotic PHT.
Sven Francque; Sam Wamutu; Shyama Chatterjee; Eric Van Marck; Arnold Herman; Albert Ramon; Alexander Jung; Wim Vermeulen; Benedicte De Winter; Paul Pelckmans; Peter Michielsen
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-10-13
Journal Detail:
Title:  Liver international : official journal of the International Association for the Study of the Liver     Volume:  30     ISSN:  1478-3231     ISO Abbreviation:  Liver Int.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-05-11     Completed Date:  2010-08-30     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101160857     Medline TA:  Liver Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  365-75     Citation Subset:  IM    
Department of Gastroenterology and Hepatology, University Hospital Antwerp, Antwerp, Belgium.
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MeSH Terms
Blood Flow Velocity
Cytokines / blood
Dose-Response Relationship, Drug
Fatty Liver / complications,  pathology,  physiopathology*
Hypertension, Portal / etiology*
Liver / metabolism,  pathology
Liver Circulation*
Peroxidase / metabolism
Phenylephrine / pharmacology
Portal Pressure*
Rats, Wistar
Splanchnic Circulation*
Vasoconstriction / drug effects
Vasoconstrictor Agents / pharmacology
Reg. No./Substance:
0/Cytokines; 0/Vasoconstrictor Agents; 59-42-7/Phenylephrine; EC

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