HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/L1452    most recent 00376.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Dull, R. O. Articles by McJames, S. Search for Related Content PubMed PubMed Citation Articles by Dull, R. O. Articles by McJames, S.

Heparan sulfates mediate pressure-induced increase in lung endothelial hydraulic conductivity via nitric oxide/reactive oxygen species

¹Department of Anesthesiology, Lung Vascular Biology Laboratory, ²Department of Bioengineering, and ³Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, School of Medicine, Salt Lake City, Utah

Submitted 22 September 2006 ; accepted in final form 27 February 2007

We investigated the nonlinear dynamics of the pressure vs. hydraulic conductivity (L_p) relationship in lung microvascular endothelial cells and demonstrate that heparan sulfates, an important component of the endothelial glycocalyx, participate in pressure-sensitive mechanotransduction that results in barrier dysfunction. The pressure vs. L_p relationship was complex, possessing both time- and pressure-dependent components. Pretreatment of lung capillary endothelial cells with heparanase III completely abolished the pressure-induced increase in L_p. This extends our (7) previous observation regarding heparan sulfates as mechanotransducers for shear stress. Inhibition of nitric oxide (NO) synthase with L-NAME (N^G-nitro-L-arginine methyl ester HCl) and intracellular scavenging of reactive oxygen species (ROS) by TBAP [tetrakis-(4-benzoic acid) porphorin] significantly attenuated the pressure-induced L_p response. Intracellular NO/ROS were visualized using the fluorescent dye, 2'7'-dichlorofluorescein diacetate (DCFA), and cells demonstrated a pressure-induced increase in intracellular fluorescence. Heparanase pretreatment significantly reduced the pressure-induced increase in intracellular fluorescence, suggesting that cell-surface heparan sulfates directly participate in mechanotransduction that results in NO/ROS production and increased permeability. This is the first report to demonstrate a role for heparan sulfates in pressure-mediated mechanotransduction and barrier regulation. These observations may have important clinical implications during conditions where pulmonary microvascular pressure is elevated.

glycocalyx; mechanotransduction

This article has been cited by other articles:

				A. R. Burns, Z. Zheng, S. H. Soubra, J. Chen, and R. E. Rumbaut Transendothelial flow inhibits neutrophil transmigration through a nitric oxide-dependent mechanism: potential role for cleft shear stress Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2904 - H2910. [Abstract] [Full Text] [PDF]