| Bioactivation of nitroglycerin and vasomotor response to nitric oxide are impaired in cirrhotic rat livers. | |
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MedLine Citation:
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PMID: 12143046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Amy A Dudenhoefer; Maurício R Loureiro-Silva; Gregory W Cadelina; Tarun Gupta; Roberto J Groszmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 36 ISSN: 0270-9139 ISO Abbreviation: Hepatology Publication Date: 2002 Aug |
Date Detail:
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Created Date: 2002-07-26 Completed Date: 2002-08-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 381-5 Citation Subset: IM |
Affiliation:
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Hepatic Hemodynamic Laboratory, VA Medical Center, West Haven, CT 06516, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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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:
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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 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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