Pentoxifylline attenuation of experimental hepatopulmonary syndrome.

Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Research Abstract Details 

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Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Abstract Text:

Junlan Zhang,Yiqun Ling,Liping Tang,Bao Luo,Balu K Chacko,Rakesh P Patel,Michael B Fallon,

Hepatopulmonary syndrome (HPS) following rat common bile duct ligation results from pulmonary molecular changes that may be influenced by circulating TNF-alpha and increased vascular shear stress, through activation of NF-kappaB or Akt. Increased pulmonary microvascular endothelin B (ET(B)) receptor and endothelial nitric oxide synthase (eNOS) levels contribute to nitric oxide production and the development of experimental HPS. Pentoxifylline (PTX), a phosphodiesterase and nonspecific TNF-alpha inhibitor, ameliorates experimental HPS when begun before hepatic injury. However, how PTX influences the molecular events associated with initiation of experimental HPS after liver injury is established is unknown. We assessed the effects of PTX on the molecular and physiological features of HPS in vivo and on shear stress or TNF-alpha-mediated events in rat pulmonary microvascular endothelial cells in vitro. PTX significantly improved HPS without altering portal or systemic hemodynamics and downregulated pulmonary ET(B) receptor levels and eNOS expression and activation. These changes were associated with a reduction in circulating TNF levels and NF-kappaB activation and complete inhibition of Akt activation. In rat pulmonary microvascular endothelial cells, PTX inhibited shear stress-induced ET(B) receptor and eNOS expression and eNOS activation. These effects were also associated with inhibition of Akt activation and were reproduced by wortmanin. In contrast, TNF-alpha had no effects on endothelial ET(B) and eNOS alterations in vitro. PTX has direct effects in the pulmonary microvasculature, likely mediated through Akt inhibition, that ameliorate experimental HPS.

Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Publishing Authors By Initials

J Zhang,Y Ling,L Tang,B Luo,BK Chacko,RP Patel,MB Fallon,

For similar vasodilation research abstracts see: vasodilation research

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Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of applied physiology (Bethesda, Md. : 198

VOLUME: 102

Page Numbers: 949-55

Journal Abbreviation: J. Appl. Physiol.

ISSN: 8750-7587

DAY: 16

MONTH: 11

YEAR: 2006

Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Information

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LANGUAGE: eng

NlmUniqueID: 8502536

Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Keywords Mesh Terms:

KEYWORDS: Vasodilation

MESH TERMS: drug effects

Chemical & Substance for Abstract: Pentoxifylline attenuation of experimental hepatopulmonary syndrome. Information

Substance Name: Proto-Oncogene Proteins c-akt

Registry Number: EC 2.7.1.37

Grant and Affiliation Information for Pentoxifylline attenuation of experimental hepatopulmonary syndrome.

AFFILIATION: University of Alabama at Birmingham, AL 35294-0005, USA.

Country: United States

AGENCY: United States NIDDK

GRANT: DK-56804

ACRONYM: DK

MEDLINETA: J Appl Physiol

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