Document Detail


Deficit in nitric oxide production in cirrhotic rat livers is located in the sinusoidal and postsinusoidal areas.
MedLine Citation:
PMID:  12490431     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intrahepatic nitric oxide (NO) production is decreased in cirrhotic livers. Our objective was to identify, in cirrhotic rat livers, intrahepatic vascular segments where the deficit of NO facilitates the effect of vasoconstrictors. By using a modified rat liver perfusion system with measurement of both the perfusion and sinusoidal (wedged hepatic vein) pressures, we studied the effect of the NO synthase blocker N(omega)-nitro-l-arginine (l-NNA) on the response to methoxamine (alpha(1)-adrenoreceptor agonist) in different segments of the intrahepatic circulation of normal and cirrhotic rat livers. l-NNA enhanced the presinusoidal, sinusoidal, and postsinusoidal responses to methoxamine in normal livers as well as the presinusoidal response in cirrhotic livers. However, l-NNA did not change the already enhanced sinusoidal/postsinusoidal response to methoxamine in cirrhotic livers. The postsinusoidal response to methoxamine was higher in cirrhotic rats with ascites than in those without ascites. We concluded that NO modulates the presinusoidal, sinusoidal, and postsinusoidal vascular tone in normal livers. NO production in cirrhotic rat livers is severely impaired in the sinusoidal and postsinusoidal areas but is preserved in the presinusoidal area, as evidenced by its normal response to l-NNA. We speculate that an increased postsinusoidal response to catecholamines may participate in the genesis of ascites in cirrhosis.
Authors:
Mauricio R Loureiro-Silva; Gregory W Cadelina; Roberto J Groszmann
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2002-12-18
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 Apr 
Date Detail:
Created Date:  2003-03-12     Completed Date:  2003-04-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G567-74     Citation Subset:  IM    
Affiliation:
Digestive Diseases Section, Yale University School of Medicine, New Haven 06520, USA.
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MeSH Terms
Descriptor/Qualifier:
Adrenergic alpha-Agonists / pharmacology
Animals
Enzyme Inhibitors / pharmacology
Liver Circulation / drug effects,  physiology*
Liver Cirrhosis / metabolism*
Male
Methoxamine / pharmacology
Microcirculation / drug effects,  physiology
Nitric Oxide / biosynthesis*
Nitric Oxide Synthase / antagonists & inhibitors,  metabolism
Nitroarginine / pharmacology
Rats
Rats, Sprague-Dawley
Vasoconstriction / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Adrenergic alpha-Agonists; 0/Enzyme Inhibitors; 10102-43-9/Nitric Oxide; 2149-70-4/Nitroarginine; 390-28-3/Methoxamine; EC 1.14.13.39/Nitric Oxide Synthase

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