Lung heparan sulfates modulate K fc during increased vascular pressure: Evidence for glycocalyx-mediated mechanotransduction

Randal O. Dull, Mark Cluff, Joseph Kingston, Denzil Hill, Haiyan Chen, Soeren Hoehne, Daniel T. Malleske, Rajwinederjit Kaur

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)L816-L828
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume302
Issue number9
DOIs
StatePublished - May 1 2012
Externally publishedYes

Fingerprint

Glycocalyx
Heparitin Sulfate
Blood Vessels
Pressure
Lung
Ventilation
Nitric Oxide
S-Nitrosoglutathione
Nitric Oxide Donors
Capillary Permeability
Artificial Respiration
Reactive Oxygen Species
Endothelial Cells
Heart Failure

Keywords

  • Endothelium
  • Permeability
  • Pulmonary edema

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Lung heparan sulfates modulate K fc during increased vascular pressure : Evidence for glycocalyx-mediated mechanotransduction. / Dull, Randal O.; Cluff, Mark; Kingston, Joseph; Hill, Denzil; Chen, Haiyan; Hoehne, Soeren; Malleske, Daniel T.; Kaur, Rajwinederjit.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 302, No. 9, 01.05.2012, p. L816-L828.

Research output: Contribution to journalArticle

Dull, Randal O. ; Cluff, Mark ; Kingston, Joseph ; Hill, Denzil ; Chen, Haiyan ; Hoehne, Soeren ; Malleske, Daniel T. ; Kaur, Rajwinederjit. / Lung heparan sulfates modulate K fc during increased vascular pressure : Evidence for glycocalyx-mediated mechanotransduction. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 2012 ; Vol. 302, No. 9. pp. L816-L828.
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