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Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver

BACKGROUND: The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats. METHODS: He...

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Autores principales: Halverscheid, Leonie, Deibert, Peter, Schmidt, René, Blum, Hubert E, Dunkern, Torsten, Pannen, Benedikt HJ, Kreisel, Wolfgang
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753560/
https://www.ncbi.nlm.nih.gov/pubmed/19765284
http://dx.doi.org/10.1186/1471-230X-9-69
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author Halverscheid, Leonie
Deibert, Peter
Schmidt, René
Blum, Hubert E
Dunkern, Torsten
Pannen, Benedikt HJ
Kreisel, Wolfgang
author_facet Halverscheid, Leonie
Deibert, Peter
Schmidt, René
Blum, Hubert E
Dunkern, Torsten
Pannen, Benedikt HJ
Kreisel, Wolfgang
author_sort Halverscheid, Leonie
collection PubMed
description BACKGROUND: The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats. METHODS: Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats. RESULTS: Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors. CONCLUSION: Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated.
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spelling pubmed-27535602009-09-29 Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver Halverscheid, Leonie Deibert, Peter Schmidt, René Blum, Hubert E Dunkern, Torsten Pannen, Benedikt HJ Kreisel, Wolfgang BMC Gastroenterol Research Article BACKGROUND: The NO - cGMP system plays a key role in the regulation of sinusoidal tonus and liver blood flow with phosphodiesterase-5 (PDE-5) terminating the dilatory action of cGMP. We, therefore, investigated the effects of PDE-5 inhibitors on hepatic and systemic hemodynamics in rats. METHODS: Hemodynamic parameters were monitored for 60 min. after intravenous injection of sildenafil and vardenafil [1, 10 and 100 μg/kg (sil1, sil10, sil100, var1, var10, var100)] in anesthetized rats. RESULTS: Cardiac output and heart rate remained constant. After a short dip, mean arterial blood pressure again increased. Systemic vascular resistance transiently decreased slightly. Changes in hepatic hemodynamic parameters started after few minutes and continued for at least 60 min. Portal (var10 -31%, sil10 -34%) and hepatic arterial resistance (var10 -30%, sil10 -32%) decreased significantly (p < 0.05). At the same time portal venous (var10 +29%, sil10 +24%), hepatic arterial (var10 +34%, sil10 +48%), and hepatic parenchymal blood flow (var10 +15%, sil10 +15%) increased significantly (p < 0.05). The fractional liver blood flow (total liver flow/cardiac output) increased significantly (var10 26%, sil10 23%). Portal pressure remained constant or tended to decrease. 10 μg/kg was the most effective dose for both PDE-5 inhibitors. CONCLUSION: Low doses of phosphodiesterase-5 inhibitors have distinct effects on hepatic hemodynamic parameters. Their therapeutic use in portal hypertension should therefore be evaluated. BioMed Central 2009-09-18 /pmc/articles/PMC2753560/ /pubmed/19765284 http://dx.doi.org/10.1186/1471-230X-9-69 Text en Copyright ©2009 Halverscheid et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Halverscheid, Leonie
Deibert, Peter
Schmidt, René
Blum, Hubert E
Dunkern, Torsten
Pannen, Benedikt HJ
Kreisel, Wolfgang
Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title_full Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title_fullStr Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title_full_unstemmed Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title_short Phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
title_sort phosphodiesterase-5 inhibitors have distinct effects on the hemodynamics of the liver
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2753560/
https://www.ncbi.nlm.nih.gov/pubmed/19765284
http://dx.doi.org/10.1186/1471-230X-9-69
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