Endothelin decreases lung edema clearance and Na,K‐ATPase activity in alveolar epithelial cells via ET‐B receptor and Nitric Oxide generation

Alejandro Comellas; Juan Litvan; Arturo Briva; Emilia Lecuona; Jiwang Chen; Jacob I Sznajder

doi:10.1096/fasebj.20.5.A1071-c

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Endothelin decreases lung edema clearance and Na,K‐ATPase activity in alveolar epithelial cells via ET‐B receptor and Nitric Oxide generation

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Endothelin decreases lung edema clearance and Na,K‐ATPase activity in alveolar epithelial cells via ET‐B receptor and Nitric Oxide generation

Alejandro Comellas, Juan Litvan, Arturo Briva, Emilia Lecuona, Jiwang Chen and Jacob I Sznajder

The FASEB journal, Vol.20(5), pp.A1071-A1071

03/2006

DOI: 10.1096/fasebj.20.5.A1071-c

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Abstract

RATIONALE ALI is characterized by high levels of endothelin‐1 (ET‐1). Administration of ET‐1 is associated with a rapid increase in edema formation. We hypothesized that ET‐1 may impair the ability of the lung to reabsorb fluid from the alveoli by inhibiting the Na,K‐ATPase. METHODS A) Isolated‐perfused rat lung model: Alveolar fluid clearance was assessed in an isolated‐perfused rat lung model by determining the concentration of Evans blue‐tagged albumin in the airspace instillate as a function of time. B) Isolated rat alveolar epithelial cells (AEC) were treated with ET‐1 to assess Na,K‐ATPase activity by a ouabain‐sensitive 86Rb+ uptake and protein analysis by Western blotting. RESULTS Isolated rat lungs perfused for 60 min with different concentrations of ET‐1 had a dose dependent decrease in alveolar fluid reabsorption. Non‐selective ET A/B receptor antagonist blocked the decrease in lung edema clearance, but not by a selective ET‐A antagonist. ET‐1 decreased alveolar fluid clearance was blocked by a nitric oxide antagonist (L‐NAME). Based on ouabain‐sensitivity curves, the endothelin‐mediated decrease in edema clearance is due predominantly to AEC type I (AECI). CONCLUSIONS These data support the hypothesis that ET‐1 impairs the ability of the lungs to clear fluid by decreasing the Na,K‐ATPase activity in AECI cells via ET‐B receptor activation and nitric oxide production, thus impairing epithelial lung recovery from lung injury. Funding: Supported by HL‐48129, T32‐HL076139 and 5F32HL071421

endothelium

lung injury

sodium transport

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Title: Subtitle: Endothelin decreases lung edema clearance and Na,K‐ATPase activity in alveolar epithelial cells via ET‐B receptor and Nitric Oxide generation
Creators: Alejandro Comellas - Midwestern State University
Juan Litvan - Midwestern University
Arturo Briva - Midwestern State University
Emilia Lecuona - Midwestern State University
Jiwang Chen - Midwestern State University
Jacob I Sznajder - Midwestern University
Resource Type: Abstract
Publication Details: The FASEB journal, Vol.20(5), pp.A1071-A1071
DOI: 10.1096/fasebj.20.5.A1071-c
ISSN: 0892-6638
eISSN: 1530-6860
Publisher: Federation of American Societies for Experimental Biology
Number of pages: 1
Language: English
Date published: 03/2006
Academic Unit: Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
Record Identifier: 9984361855402771

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