Evidence map›Paper›PMID 18948426›Full record

ArticleAmerican journal of respiratory and critical care medicine2009

Endothelin-1 impairs alveolar epithelial function via endothelial ETB receptor.

Alejandro P Comellas, Arturo Briva, Laura A Dada, Maria L Butti, Humberto E Trejo, Cecilia Yshii, Zaher S Azzam, Juan Litvan, Jiwang Chen, Emilia Lecuona and 3 more

Open access · greenAbstract read
In one paragraph

Article in American journal of respiratory and critical care medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 44 citations in OpenAlex.

  1. Trial
  2. Ischemic Stroke in a Child after a Probable Scorpion Sting: Correspondence.The American journal of tropical medicine and hygiene · 2025
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  12. Uncommon presentation of scorpion sting at teaching hospital.Journal of family medicine and primary care · 2020
    Article
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  18. Article
  19. Lung Edema Clearance: Relevance to Patients with Lung Injury.Rambam Maimonides medical journal · 2015
    Article
  20. Macitentan for the treatment of pulmonary arterial hypertension.Vascular health and risk management · 2014
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 4 countries.

Alejandro P ComellasDivision of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA. alejandro-comellas@uiowa.edu
Arturo Briva
Laura A Dada
Maria L Butti
Humberto E Trejo
Cecilia Yshii
Zaher S Azzam
Juan Litvan
Jiwang Chen
Emilia Lecuona
Liuska M Pesce
Masashi Yanagisawa
Jacob I Sznajder
Northwestern University · USTechnion – Israel Institute of Technology · ILThe University of Texas Southwestern Medical Center · USUniversidad de la República de Uruguay · UY

Funding

ROLE AND REGULATION OF SODIUM, POTASSIUM ATPASE IN LUNGR01HL048129 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI SZNAJDER, JACOB I · 1996 to 2007
$2.7M
Hypoxia Disrupts the Alveolar Barrier: Role of ClaudinsK01HL080966 · NHLBI · UNIVERSITY OF IOWA · PI COMELLAS, ALEJANDRO PIERRE · 2006 to 2010
$665k
NHLBI NIH HHS K01HL080966-01NHLBI NIH HHS R01 HL048129-14
6 · The paper itself

Abstract

rationaleEndothelin-1 (ET-1) is increased in patients with high-altitude pulmonary edema and acute respiratory distress syndrome, and these patients have decreased alveolar fluid reabsorption (AFR).

objectivesTo determine whether ET-1 impairs AFR via activation of endothelial cells and nitric oxide (NO) generation.

methodsIsolated perfused rat lung, transgenic rats deficient in ETB receptors, coincubation of lung human microvascular endothelial cells (HMVEC-L) with rat alveolar epithelial type II cells or A549 cells, ouabain-sensitive 86Rb+ uptake. MEASUREMENTS AND MAIN

resultsThe ET-1-induced decrease in AFR was prevented by blocking the endothelin receptor ETB, but not ETA. Endothelial-epithelial cell interaction is required, as direct exposure of alveolar epithelial cells (AECs) to ET-1 did not affect Na,K-ATPase function or protein abundance at the plasma membrane, whereas coincubation of HMVEC-L and AECs with ET-1 decreased Na,K-ATPase activity and protein abundance at the plasma membrane. Exposing transgenic rats deficient in ETB receptors in the pulmonary vasculature (ET-B(-/-)) to ET-1 did not decrease AFR or Na,K-ATPase protein abundance at the plasma membrane of AECs. Exposing HMVEC-L to ET-1 led to increased NO, and the ET-1-induced down-regulation of Na,K-ATPase was prevented by the NO synthase inhibitor l-NAME, but not by a guanylate cyclase inhibitor.

conclusionsWe provide the first evidence that ET-1, via an endothelial-epithelial interaction, leads to decreased AFR by a mechanism involving activation of endothelial ETB receptors and NO generation leading to alveolar epithelial Na,K-ATPase down-regulation in a cGMP-independent manner.

Indexed as

Adenosine TriphosphatasesAnimalsCyclic GMPDisease Models, AnimalEndothelin-1Endothelium, VascularExtravascular Lung WaterFemaleHumansIn Vitro TechniquesLung InjuryMaleNitric OxidePulmonary AlveoliRatsRats, TransgenicAdenosine TriphosphatasesCyclic GMPEndothelin-1Nitric OxideReceptor, Endothelin AReceptor, Endothelin B

Identifiers

PMID18948426
PMCPMC2633058
OpenAlexW2127455984

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.