Heparin impairs glycocalyx barrier properties and attenuates shear dependent vasodilation in mice

Jurgen W.G.E. VanTeeffelen*, Judith Brands, Carin Jansen, Jos A.E. Spaan, Hans Vink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

52 Citations (Scopus)
4 Downloads (Pure)

Abstract

The endothelial glycocalyx is a hydrated mesh of polysaccharides and adsorbed plasma proteins that forms the true interface between the flowing blood and the endothelium. We hypothesized in the present study that competitive binding of heparin to glycocalyx-associated proteins would affect glycocalyx barrier properties and mechanotransduction of shear stress to the endothelium. In anesthetized mice, the clearance of 70-kDa dextrans from the circulation was increased (P<0.05 versus saline) 1 hour after heparin (1.25 U) and glycocalyx degradation with hyaluronidase (35 U; amount cleared in 30 minutes after saline: 11±5%; after heparin: 45±8%; after hyaluronidase: 30±3%). Clearance of 40-kDa dextrans increased (P<0.05 versus saline) to a lesser extent after both treatments (saline: 46±3%; heparin: 60±5%; hyaluronidase: 60±2%). The dilator response of second-order arterioles in cremaster muscle during reactive hyperemia was reduced for ≤90 minutes after heparin as reflected by a decrease (P=0.008) in t50 of diameter recovery, and this effect was associated with a diminished NO bioavailability. Infusion of hyaluronidase resulted in reductions (P<0.05) in baseline and peak reactive hyperemic diameter, whereas, despite an increase in wall shear rate at the beginning of reactive hyperemia, t50 of diameter recovery was not affected. In conclusion, our data in mice show that a heparin challenge is associated with increased vascular leakage of dextrans and impaired arteriolar vasodilation during reactive hyperemia. Our data suggest that protein-heparan sulfate interactions are important for a functional glycocalyx.

Original languageEnglish
Pages (from-to)261-267
Number of pages7
JournalHypertension
Volume50
Issue number1
DOIs
Publication statusPublished - 1 Jul 2007
Externally publishedYes

Keywords

  • Glycocalyx
  • Heparin
  • Hyaluronidase
  • Mechanotransduction
  • Reactive hyperemia

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