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Am J Physiol Heart Circ Physiol (June 17, 2005). doi:10.1152/ajpheart.00218.2005
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Submitted on March 7, 2005
Accepted on June 15, 2005

Atrial natriuretic peptide induces shedding of the endothelial glycocalyx in the coronary vascular bed of guinea pig hearts

Dirk Bruegger1, Matthias Jacob1, Markus Rehm2*, Michael Loetsch3, Ulrich Welsch4, Peter Conzen2, and Bernhard F Becker3

1 Clinic for Anesthesiology, Ludwig-Maximilians-University, Munich, Germany; Institute of Physiology, Ludwig-Maximilians-University, Munich, Germany
2 Clinic for Anesthesiology, Ludwig-Maximilians-University, Munich, Germany
3 Institute of Physiology, Ludwig-Maximilians-University, Munich, Germany
4 Deaprtment of Anatomy, Ludwig-Maximilians-University, Munich, Germany

* To whom correspondence should be addressed. E-mail: markus.rehm{at}med.uni-muenchen.de.

Atrial natriuretic peptide (ANP) is reported to enhance vascular permeability in vivo. Our aim was to evaluate the impact of ANP on coronary extravasation of fluids and macromolecules and on the integrity of the endothelial glycocalyx. Isolated guinea pig hearts (n=6 per group) were perfused with Krebs-Henseleit buffer in a Langendorff mode. A 6% hydroxyethyl starch (HES) solution was infused into the coronary system for 20 min without (Control) and simultaneously with ANP at 10-9 M (ANP). In two further series, the glycocalyx was enzymatically degraded by means of heparinase application (10 IU over 15 min), followed again by the infusion of HES in the absence (HEP) and presence of ANP (ANP with HEP). Net fluid filtration, extravasation of HES, electron microscopic visualization of the glycocalyx, and quantification of shedding of syndecan-1, a component of the glycocalyx, were determined. In the groups ANP, ANP with HEP, and HEP an increase in fluid leak was observed (+29%, +31%, +14%, respectively), whereas Control decreased (-13%). Similarly, an accelerated extravasation of colloid was observed in these 3 groups. Coronary release of syndecan-1 increased 9 to 18-fold during infusion of ANP. Electron microscopy revealed a dramatic degradation of the glycocalyx after ANP. These results indicate that the endothelial glycocalyx serves as a barrier to transmural exchange of fluid and colloid in the coronary vascular system. ANP causes rapid shedding of individual components of the glycocalyx and histologically detectable degradation. Thus, the permeability increasing effect of ANP may at least be partially related to changes in the integrity of the endothelial glycocalyx.




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