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Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability

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Abstract

Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations. This study investigates the impact and mechanism of action of physiological doses of ANP and related peptides on the vascular barrier. In isolated guinea pig hearts, prepared and perfused in a modified Langendorff mode with and without the intravascular presence of the colloid hydroxyethyl starch (HES), we measured functional changes in vascular permeability and glycocalyx shedding related to intracoronary infusion of physiological concentrations of A-, B- and C-type natriuretic peptide (ANP, BNP and CNP). Significant coronary venous washout of glycocalyx constituents (syndecan-1 and heparan sulfate) was observed. As tested for ANP, this effect was positively related to the intracoronary concentration. Intravascular shedding of the glycocalyx was morphologically confirmed by electron microscopy. Also, functional vascular barrier competence decreased, as indicated by significant increases in transudate formation and HES extravasation. Ortho-phenanthroline, a non-specific inhibitor of matrix metalloproteases, was able to reduce ANP-induced glycocalyx shedding. These findings suggest participation of natriuretic peptides in pathophysiological processes like heart failure, inflammation or sepsis. Inhibition of metalloproteases might serve as a basis for future therapeutical options.

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Acknowledgments

The authors are very grateful to Dr. Barbara Jacob for expert statistical assistance. The study was performed using departmental resources of the Department of Anesthesiology, University Hospital Munich, Germany and the Walter-Brendel-Centre of Experimental Medicine, LMU Munich, Germany.

Conflicts of interest

None of the authors have any conflicts of interest in connection with this work.

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Authors and Affiliations

  1. Department of Anesthesiology, University Hospital Munich, Nussbaumstrasse 20, 80336, Munich, Germany

    Matthias Jacob, Thomas Saller, Daniel Chappell & Markus Rehm

  2. Institute for Cell Biology, LMU Munich Schillerstrasse 42, 80336, Munich, Germany

    Ulrich Welsch

  3. Walter-Brendel-Centre of Experimental Medicine, LMU Munich Schillerstrasse 44, 80336, Munich, Germany

    Bernhard F. Becker

Authors
  1. Matthias Jacob
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  2. Thomas Saller
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  3. Daniel Chappell
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  5. Ulrich Welsch
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  6. Bernhard F. Becker
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Correspondence to Matthias Jacob.

Additional information

M. Jacob and T. Saller contributed equally to this work.

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Jacob, M., Saller, T., Chappell, D. et al. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability. Basic Res Cardiol 108, 347 (2013). https://doi.org/10.1007/s00395-013-0347-z

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  • DOI: https://doi.org/10.1007/s00395-013-0347-z

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