ISSN |
1007-9327 (print) and 2219-2840 (online) |
Open Access |
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
Copyright |
© The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved. |
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Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
Website |
http://www.wjgnet.com |
Category |
Gastroenterology & Hepatology |
Manuscript Type |
Basic Study |
Article Title |
Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension
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Manuscript Source |
Invited Manuscript |
All Author List |
Denise Schaffner, Adhara Lazaro, Peter Deibert, Peter Hasselblatt, Patrick Stoll, Lisa Fauth, Manfred W Baumstark, Irmgard Merfort, Annette Schmitt-Graeff and Wolfgang Kreisel |
ORCID |
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Funding Agency and Grant Number |
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Corresponding Author |
Wolfgang Kreisel, MD, Emeritus Professor, Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, Faculty of Medicine, University of Freiburg, Hugstetter Str. 55, Freiburg 79106, Germany. wolfgang.kreisel@uniklinik-freiburg.de |
Key Words |
Portal hypertension; Thioacetamide; Nitric oxide; Liver cirrhosis; Cyclic guanosine monophosphate; Phosphodiesterase-5; Sildenafil; Hepatic stellate cells; Metabolic zonation |
Core Tip |
A constriction of sinusoids plays an important role in the pathogenesis of cirrhotic portal hypertension, wherein the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a pivotal role. In a rat model of liver cirrhosis phosphodiesterase-5 (PDE-5) was markedly overexpressed both on the mRNA and the protein level. PDE-5 converts the vasodilating cGMP to inactive 5’-GMP. In healthy liver a zonation of PDE-5 was found which is abrogated in cirrhosis. Serum cGMP was reduced in cirrhosis. Inhibition of PDE-5 by Sildenafil normalized serum cGMP levels and lowered portal venous pressure. Hence, the inhibition of PDE-5 may be a promising adjunct in portal hypertension therapy. |
Publish Date |
2018-10-12 05:32 |
Citation |
Schaffner D, Lazaro A, Deibert P, Hasselblatt P, Stoll P, Fauth L, Baumstark MW, Merfort I, Schmitt-Graeff A, Kreisel W. Analysis of the nitric oxide-cyclic guanosine monophosphate pathway in experimental liver cirrhosis suggests phosphodiesterase-5 as potential target to treat portal hypertension. World J Gastroenterol 2018; 24(38): 4356-4368 |
URL |
http://www.wjgnet.com/1007-9327/full/v24/i38/4356.htm |
DOI |
http://dx.doi.org/10.3748/wjg.v24.i38.4356 |