| A distinct nitric oxide and adenosine A1 receptor dependent hepatic artery vasodilatatory response in the CCl-cirrhotic liver. | |
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MedLine Citation:
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PMID: 20500549 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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METHODS: Cirrhosis was induced by CCl(4). Using a bivascular liver perfusion dose-response curves to adenosine of the HA were performed in the presence and the absence of pan-adenosine blocker (8-SPT), A1 blocker (caffeine) or nitric oxide synthase-blocker (l-NMMA) after preconstriction with an alpha1-agonist (methoxamine). Western blot of the HA were used to measure the density of the A1 and A2a receptors. RESULTS: Adenosine caused a dose dependent relaxation of the hepatic artery of both cirrhotic and control animals that were blocked in both groups by 8-SPT (P<0.02). The response to adenosine was greater in cirrhotic rats (P=0.016). Both l-NMMA (P=0.003) and caffeine reduced the response to adenosine in cirrhotic but not in control animals. Western blot analysis showed a higher density of A1 and a lower density of A2a receptor in cirrhotic animals (P<0.05). CONCLUSION: The adenosine-induced vasodilatation of the HA is increased in cirrhotic rats suggesting a role for adenosine-NO in the decreased hepatic arterial vascular resistance found in cirrhosis. This significantly greater response in cirrhosis by the A1 receptor follows the same pathway that is seen in hypoxic conditions in extra-hepatic tissues. |
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Authors:
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Alexander Zipprich; Wajahat Z Mehal; Cristina Ripoll; Roberto J Groszmann |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-05-24 |
Journal Detail:
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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 Aug |
Date Detail:
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Created Date: 2010-07-26 Completed Date: 2010-11-02 Revised Date: 2011-12-21 |
Medline Journal Info:
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Nlm Unique ID: 101160857 Medline TA: Liver Int Country: England |
Other Details:
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Languages: eng Pagination: 988-94 Citation Subset: IM |
Affiliation:
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Digestive Disease Section, Yale University School of Medicine, New Haven, CT, USA. alexander.zipprich@medizin.uni-halle.de |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine
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pharmacology Adenosine A1 Receptor Antagonists Animals Blotting, Western Caffeine / pharmacology Carbon Tetrachloride* Disease Models, Animal Dose-Response Relationship, Drug Enzyme Inhibitors / pharmacology Hepatic Artery / drug effects, metabolism*, physiopathology Liver Cirrhosis, Experimental / chemically induced, metabolism*, physiopathology Male Nitric Oxide / metabolism* Nitric Oxide Synthase / antagonists & inhibitors, metabolism Perfusion Portal Vein / physiopathology Rats Rats, Sprague-Dawley Receptor, Adenosine A1 / metabolism* Receptor, Adenosine A2A / metabolism Theophylline / analogs & derivatives, pharmacology Vascular Resistance Vasodilation* / drug effects Vasodilator Agents / pharmacology omega-N-Methylarginine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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R01 DK076674-04/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Adenosine A1 Receptor Antagonists; 0/Enzyme Inhibitors; 0/Receptor, Adenosine A1; 0/Receptor, Adenosine A2A; 0/Vasodilator Agents; 10102-43-9/Nitric Oxide; 17035-90-4/omega-N-Methylarginine; 56-23-5/Carbon Tetrachloride; 58-08-2/Caffeine; 58-55-9/Theophylline; 58-61-7/Adenosine; 80206-91-3/8-(4-sulfophenyl)theophylline; EC 1.14.13.39/Nitric Oxide Synthase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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