Document Detail


Lung heparan sulfates modulate K(fc) during increased vascular pressure: evidence for glycocalyx-mediated mechanotransduction.
MedLine Citation:
PMID:  22160307     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lung endothelial cells respond to changes in vascular pressure through mechanotransduction pathways that alter barrier function via non-Starling mechanism(s). Components of the endothelial glycocalyx have been shown to participate in mechanotransduction in vitro and in systemic vessels, but the glycocalyx's role in mechanosensing and pulmonary barrier function has not been characterized. Mechanotransduction pathways may represent novel targets for therapeutic intervention during states of elevated pulmonary pressure such as acute heart failure, fluid overload, and mechanical ventilation. Our objective was to assess the effects of increasing vascular pressure on whole lung filtration coefficient (K(fc)) and characterize the role of endothelial heparan sulfates in mediating mechanotransduction and associated increases in K(fc). 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 roles of heparan sulfates, nitric oxide, and reactive oxygen species were investigated. Increases in capillary pressure altered K(fc) in a nonlinear relationship, suggesting non-Starling mechanism(s). nitro-l-arginine methyl ester and heparanase III attenuated the effects of increased capillary pressure on K(fc), demonstrating active mechanotransduction leading to barrier dysfunction. The nitric oxide (NO) donor S-nitrosoglutathione exacerbated pressure-mediated increase in K(fc). Ventilation strategies altered lung NO concentration and the K(fc) response to increases in vascular pressure. This is the first study to demonstrate a role for the glycocalyx in whole lung mechanotransduction and has important implications in understanding the regulation of vascular permeability in the context of vascular pressure, fluid status, and ventilation strategies.
Authors:
Randal O Dull; Mark Cluff; Joseph Kingston; Denzil Hill; Haiyan Chen; Soeren Hoehne; Daniel T Malleske; Rajwinederjit Kaur
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2011-12-09
Journal Detail:
Title:  American journal of physiology. Lung cellular and molecular physiology     Volume:  302     ISSN:  1522-1504     ISO Abbreviation:  Am. J. Physiol. Lung Cell Mol. Physiol.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-02     Completed Date:  2012-06-29     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901229     Medline TA:  Am J Physiol Lung Cell Mol Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  L816-28     Citation Subset:  IM    
Affiliation:
Department of Anesthesiology, Lung Vascular Biology Laboratory, University of Utah School of Medicine, Salt Lake City, UT 84132-2304, USA. randal.dull@hsc.utah.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Atrial Function, Left / drug effects
Blood Pressure
Glucuronidase / pharmacology
Glycocalyx / metabolism,  physiology*
Heparitin Sulfate / metabolism,  physiology*
Lung / drug effects,  metabolism,  physiology*
Male
Mechanotransduction, Cellular*
NG-Nitroarginine Methyl Ester / pharmacology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / antagonists & inhibitors,  metabolism
Permeability / drug effects
Porphyrins / pharmacology
Pulmonary Ventilation
Rats
Rats, Sprague-Dawley
S-Nitrosoglutathione / pharmacology
Tidal Volume
Tyrosine / analogs & derivatives,  metabolism
Grant Support
ID/Acronym/Agency:
5R01HL085255-04/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Porphyrins; 0/tetrakis(4-benzoic acid)porphyrin; 10102-43-9/Nitric Oxide; 3604-79-3/3-nitrotyrosine; 50903-99-6/NG-Nitroarginine Methyl Ester; 55520-40-6/Tyrosine; 57564-91-7/S-Nitrosoglutathione; 9050-30-0/Heparitin Sulfate; EC 1.14.13.39/Nitric Oxide Synthase Type III; EC 1.14.13.39/Nos3 protein, rat; EC 3.2.1.-/heparanase; EC 3.2.1.31/Glucuronidase
Comments/Corrections

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