| Lung heparan sulfates modulate filtration coefficient (Kfc) during increased vascular pressure; evidence for glyocalyx mediated mechano-transduction. | |
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MedLine Citation:
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PMID: 22160307 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Abstract Rationale: Lung endothelial cells respond to changes in vascular pressure through mechano-transduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechano-transduction in vitro and in systemic vessels, but the glycocalyx's role in mechano-sensing and pulmonary barrier function has not been characterized. Mechano-transduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload and mechanical ventilation. Objective: Assess the effects of increasing vascular pressure on whole lung filtration coefficient (K(fc)) and characterize the role of endothelial heparan sulfates in mediating mechano-transduction and associated increases in K(fc). Methods: Isolated perfused rat lung preparation was used to measure K(fc) in response to changes in vascular pressure in combination with superimposed changes in airway pressure. The role of heparan sulfates, nitric oxide and reactive oxygen species were investigated. Measurements and Main Results: Increases in capillary pressure altered K(fc) in a non-linear relationship, suggesting non-Starling mechanism(s). L-NAME and heparanase III attenuated the effects of increased capillary pressure on K(fc), demonstrating active mechano-transduction leading to barrier dysfunction. The nitric oxide (NO) donor, GSNO, exacerbated pressure mediated increase in K(fc). Ventilation strategies altered lung NO concentration and the K(fc) response to increases in vascular pressure. Conclusions: This is the first study to demonstrate a role for the glycocalyx in whole lung mechano-transduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status and ventilation strategies. |
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Authors:
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Randal O Dull; Mark Cluff; Joseph Kingston; Denzil Hill; Haiyan Chen; Soeren Hoehne; Daniel Thomas Malleske; Rajwinderjit Kaur |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-9 |
Journal Detail:
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Title: American journal of physiology. Lung cellular and molecular physiology Volume: - ISSN: 1522-1504 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901229 Medline TA: Am J Physiol Lung Cell Mol Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1University of Utah. |
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