| Increased phosphodiesterase-5 expression is involved in the decreased vasodilator response to nitric oxide in cirrhotic rat livers. | |
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MedLine Citation:
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PMID: 16545481 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND/AIMS: Cirrhotic livers have a deficient vasodilator response to nitric oxide (NO). The vasodilator effect of NO is normally limited by the degradation of its second messenger cyclic guanosine 3', 5' monophosphate by phosphodiesterases. We investigated (1) the phosphodiesterase-5 (PDE-5) expression in normal and cirrhotic rat livers, (2) the location of the deficient response to NO in cirrhotic livers, and (3) the effect of the PDE-5 inhibitor Sildenafil citrate on this deficient response. METHODS: Normal and ascitic cirrhotic rats were subjected to liver perfusion with continuous measurement of both perfusion and sinusoidal (wedge hepatic) pressures. After incubation with N-monomethyl-l-arginine and pre-constriction with Methoxamine, concentration-response curves to the spontaneous NO donor S-nitroso-N-acetylpenicillamine were obtained in the absence or presence of Sildenafil (10(-8)M). RESULTS: PDE-5 expression (Western blot) in cirrhotic livers was higher than in normal livers (P=0.042). Compared to normal livers, cirrhotic livers showed a decreased response to S-nitroso-N-acetylpenicillamine in the pre-sinusoidal area (P=0.003) but not in the sinusoidal/post-sinusoidal area (P=0.433). In the presence of Sildenafil, normal and cirrhotic livers showed similar pre-sinusoidal (P=0.419) and sinusoidal/post-sinusoidal (P=0.875) responses to S-nitroso-N-acetylpenicillamine. CONCLUSIONS: Increased PDE-5 expression is involved in the decreased vascular response to NO in cirrhotic livers. |
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Authors:
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Mauricio R Loureiro-Silva; Yasuko Iwakiri; Juan G Abraldes; Omar Haq; Roberto J Groszmann |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. Date: 2006-02-28 |
Journal Detail:
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Title: Journal of hepatology Volume: 44 ISSN: 0168-8278 ISO Abbreviation: J. Hepatol. Publication Date: 2006 May |
Date Detail:
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Created Date: 2006-04-17 Completed Date: 2006-09-27 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8503886 Medline TA: J Hepatol Country: England |
Other Details:
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Languages: eng Pagination: 886-93 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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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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3',5'-Cyclic-GMP Phosphodiesterases Animals Cyclic Nucleotide Phosphodiesterases, Type 5 Enzyme Inhibitors / pharmacology Liver Circulation / physiology Liver Cirrhosis / metabolism*, physiopathology* Male Nitric Oxide / metabolism* Nitric Oxide Synthase / antagonists & inhibitors, metabolism Phosphodiesterase Inhibitors / pharmacology Phosphoric Diester Hydrolases / metabolism* Piperazines / pharmacology Purines Rats Rats, Sprague-Dawley Sulfones Vasodilation / physiology* omega-N-Methylarginine / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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KO1 DK067933-01/DK/NIDDK NIH HHS; P30 DK04989/DK/NIDDK NIH HHS; P30 DK34989/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Enzyme Inhibitors; 0/Phosphodiesterase Inhibitors; 0/Piperazines; 0/Purines; 0/Sulfones; 10102-43-9/Nitric Oxide; 139755-83-2/sildenafil; 17035-90-4/omega-N-Methylarginine; EC 1.14.13.39/Nitric Oxide Synthase; EC 3.1.4.-/Phosphoric Diester Hydrolases; EC 3.1.4.35/3',5'-Cyclic-GMP Phosphodiesterases; EC 3.1.4.35/Cyclic Nucleotide Phosphodiesterases, Type 5; EC 3.1.4.35/Pde5a protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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