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 ϭ 6/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 group) and simultaneously with (ANP group) ANP at 10 Ϫ9 M. In two further series, the glycocalyx was enzymatically degraded by means of heparinase (Hep) application (10 IU over 15 min), followed again by the infusion of HES in the absence (Hep group) and presence (ANPϩHep group) of ANP. 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. An increase in fluid leak was observed in ANP, ANPϩHep, and Hep hearts [ϩ29%, ϩ31%, ϩ14%, respectively; a decrease was observed in Control hearts (Ϫ13%)]. Similarly, an accelerated extravasation of colloid was observed in these three 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 be at least partially related to changes in the integrity of the endothelial glycocalyx.

Background: Shear stress induces coronary dilatation via production of nitric oxide (NO). This should involve the endothelial glycocalyx (EG). A greater effect was expected of albumin versus hydroxyethyl starch (HES) perfusion, because albumin seals coronary leaks more effectively than HES in an EG-dependent way. Methods: Isolated hearts (guinea pigs) were perfused at constant pressure with Krebs-Henseleit buffer augmented with 1/3 volume 5% human albumin or 6% HES (200/0.5 or 450/0.7). Coronary flow was also determined after EG digestion (heparinase) and with nitro-L-arginine (NO-L-Ag). Results: Coronary flow (9.50 ± 1.09, 5.10 ± 0.49, 4.87 ± 1.19 and 4.15 ± 0.09 ml/min/g for ‘albumin’, ‘HES 200’, ‘HES 450’ and ‘control’, respectively, n = 5–6) did not correlate with perfusate viscosity (0.83, 1.02, 1.24 and 0.77 cP, respectively). NO-L-Ag and heparinase diminished dilatation by albumin, but not additively. Alone NO-L-Ag suppressed coronary flow during infusion of HES 450. Electron microscopy revealed a coronary EG of 300 nm, reduced to 20 nm after heparinase. Cultured endothelial cells possessed an EG of 20 nm to begin with. Conclusions: Albumin induces greater endothelial shear stress than HES, despite lower viscosity, provided the EG contains negative groups. HES 450 causes some NO-mediated dilatation via even a rudimentary EG. Cultured endothelial cells express only a rudimentary glycocalyx, limiting their usefulness as a model system.

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