Document Detail


Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers.
MedLine Citation:
PMID:  12143046     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Nitroglycerin (NTG), a nitric oxide (NO) donor, has been shown to reduce portal pressure in cirrhotic patients. Using the in situ perfusion of normal and cirrhotic rat livers, we compared the vascular relaxation induced by either NTG or the spontaneous nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP). Normal and cirrhotic livers were perfused (40 mL/min, 37 degrees C) with Krebs' solution in a recirculating system. After preconstriction with methoxamine (10(-4) mol/L), a dose-response study was performed using 6 cumulative doses of NTG or SNAP (10(-7) to 3 x 10(-5) mol/L). NO(x) (NO(-)(2) + NO(-)(2) production in the perfusate was measured by chemiluminescence. Cirrhotic livers exhibited lower vasorelaxant responses, compared with normal livers, to both NTG (P <.0001) and SNAP (P =.0020). In normal livers, NTG and SNAP induced similar vasorelaxant responses (P =.44). In cirrhotic livers, NTG induced less vasorelaxation than SNAP (P <.0001). In the presence of NTG (P =.0045), but not SNAP (P =.99), NO(x) production in experiments with cirrhotic livers was lower than in experiments with normal livers. In conclusion, in cirrhotic rat livers, the vasorelaxant response to NTG is impaired owing to both a decreased metabolism of this NO donor and an inability of the hepatic vasculature to respond to NO.
Authors:
Amy A Dudenhoefer; Maurício R Loureiro-Silva; Gregory W Cadelina; Tarun Gupta; Roberto J Groszmann
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  36     ISSN:  0270-9139     ISO Abbreviation:  Hepatology     Publication Date:  2002 Aug 
Date Detail:
Created Date:  2002-07-26     Completed Date:  2002-08-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  381-5     Citation Subset:  IM    
Affiliation:
Hepatic Hemodynamic Laboratory, VA Medical Center, West Haven, CT 06516, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Liver / metabolism,  pathology
Liver Cirrhosis, Experimental / drug therapy*,  metabolism*,  pathology
Male
Nitrates / metabolism
Nitric Oxide / metabolism*
Nitric Oxide Donors / pharmacology
Nitrites / metabolism
Nitroglycerin / metabolism*,  pharmacology
Organ Size
Rats
Rats, Sprague-Dawley
S-Nitroso-N-Acetylpenicillamine / pharmacology
Vasodilator Agents / metabolism*,  pharmacology
Chemical
Reg. No./Substance:
0/Nitrates; 0/Nitric Oxide Donors; 0/Nitrites; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 55-63-0/Nitroglycerin; 79032-48-7/S-Nitroso-N-Acetylpenicillamine

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