Document Detail


Endothelial dysfunction and decreased production of nitric oxide in the intrahepatic microcirculation of cirrhotic rats.
MedLine Citation:
PMID:  9755227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Increased intrahepatic resistance in cirrhotic livers is in part caused by increased vascular tone. Several morphological abnormalities have been described in the sinusoidal endothelial cells of cirrhotic livers, but the functional impact of these abnormalities on the intrahepatic vascular tone has not been studied. The aim of this study was to investigate the intrahepatic endothelial function and the role of nitric oxide (NO) with regard to vascular tone in cirrhotic livers. Isolated rat liver perfusions were performed in cirrhotic rats (induced by chronic carbon tetrachloride inhalation) and weight-matched normal controls. After preconstricting the intrahepatic microcirculation with methoxamine (10(-4) mol/L), response to cumulative doses of receptor-mediated endothelial agonist, acetylcholine (10(-7) mol/L-10(-5) mol/L), was obtained. In another series, response to the receptor-independent endothelial agonist, calcium ionophore A23187 (10(-7) mol/L and 3 x 10(-7) mol/L), was obtained in the absence and presence of Nomega-nitro-L-arginine (NNA) and indomethacin. In a third series of rats, nitrate and nitrite production was measured in the perfusate of perfused normal and cirrhotic livers. There was significantly less vasorelaxation in cirrhotic livers as compared with normal livers in response to acetylcholine and calcium ionophore A23187 (P < .0001). The impaired vasorelaxation was a result of a decrease in both NO-mediated and non-NO-mediated components of vasorelaxation. Cirrhotic livers from ascitic rats had significantly less vasorelaxation as compared with livers from nonascitic rats (P < .005). There was significantly less production of nitrates and nitrites in cirrhotic livers (P < .05). The liver microcirculation of cirrhotic livers is characterized by endothelial dysfunction that results in impaired release of endothelial relaxing factors including NO.
Authors:
T K Gupta; M Toruner; M K Chung; R J Groszmann
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  28     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  1998 Oct 
Date Detail:
Created Date:  1998-11-05     Completed Date:  1998-11-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  926-31     Citation Subset:  IM    
Affiliation:
Hepatic Hemodynamic Laboratory, VA Medical Center, West Haven, CT 06516, USA.
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MeSH Terms
Descriptor/Qualifier:
Acetylcholine / pharmacology
Animals
Calcimycin / pharmacology
Carbon Tetrachloride Poisoning / complications
Endothelium, Vascular / physiology,  physiopathology*
Indomethacin / pharmacology
Liver Circulation / physiology*
Liver Cirrhosis, Experimental / blood,  chemically induced,  physiopathology*
Male
Methoxamine / pharmacology
Microcirculation / drug effects,  physiology,  physiopathology*
Muscle, Smooth, Vascular / drug effects,  physiology,  physiopathology
Nitrates / blood
Nitric Oxide / biosynthesis*
Nitrites / blood
Nitroarginine / pharmacology
Perfusion
Rats
Rats, Sprague-Dawley
Reference Values
Vasodilation / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Nitrates; 0/Nitrites; 10102-43-9/Nitric Oxide; 2149-70-4/Nitroarginine; 390-28-3/Methoxamine; 51-84-3/Acetylcholine; 52665-69-7/Calcimycin; 53-86-1/Indomethacin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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