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

Abstract

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.

State of the art in fluid and volume therapy

“…It is important to realize that the blood volume can only increase slightly due to infusions [24]. ANP is released immediately, the vascular barrier becomes permeable, and the blood volume quickly returns to normal high [25][26][27]74]. In the case of larger blood losses, a moderate -sometimes considerable, as demonstrated by the presented example -hypovolemia is much more frequent, caused by an apparently generous but in fact inadequate volume therapy.…”

“…Volume loading is associated with small volume effects, but also with adverse events [24]. This owes to the fact that volume loading (infusion in the absence of corresponding fluid loss) causes expansion of the atria and thus release of atrial natriuretic peptide (ANP) [25][26][27]. This peptide alters the endothelial glycocalyx, thus, increasing extravasation of macromolecules (colloids) and fluid.…”

The endothelial glycocalyx: a review of the vascular barrier

“…In isolated guinea pig hearts, an infusion of ANP increased the extravasation of colloid. Moreover, ANP degrades the coronary endothelial surface layer, causing rapid shedding of syndecan core protein [24]. In patients who had acute hypervolaemic haemodilution as a pre-emptive blood-saving measure, 60% of the infused volume leaked into the interstitial space within minutes [25].…”

Damage of the Endothelial Glycocalyx in Dialysis Patients

“…5 It is involved in mediating shear-induced release of nitric oxide and contributes to the endothelial permeability barrier, the regulation of redox state, and the inhibition of coagulation as well as leukocyte and platelet adhesion. [6][7][8][9] Perturbation of glycocalyx occurs after provocation with inflammatory or atherogenic stimuli (such as ischemia reperfusion, 10 infusion of oxidized LDL, 9,11 administration of TNFa 12 or endotoxin, 13 and during hyperglycemia 14 ) and after stimulation with thrombin, 15 atrial natriuretic peptide, 16 or abnormal blood shear stress. 17,18 Consequences of glycocalyx perturbation include a wide range of vascular abnormalities in experimental models, including increased vascular permeability followed by generation of tissue edema, 19 increased rolling and adhesion of leukocytes, 6 and increased platelet adhesion.…”