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

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.

Syndecan-1 in Acute Decompensated Heart Failure – Association With Renal Function and Mortality –

“…In experimental models, natriuretic peptides augment the level of endothelium glycocalyx biomarkers (including syndecan-1) and increase endothelium permeability. 31 Although degradation of the mouse endothelial glycocalyx increases the number of leukocytes adhered to the vessel walls, 32 we did not find any correlation between syndecan-1 and other biomarkers of endothelial activation and function (eg, ICAM-1 and NOx).…”

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.…”

Endothelial Actions of ANP Enhance Myocardial Inflammatory Infiltration in the Early Phase After Acute Infarction

“…26 Because disruption of the glycocalyx favors postischemic neutrophil adhesion, we hypothesized that shedding of the glycocalyx by endogenously released NPs contributes to myocardial inflammatory infiltration after AMI. By fluorescent hyaluronan staining, the apical endothelial glycocalyx was clearly detectable in the hearts of sham-operated control mice and was indeed thinner and reduced ≈50% after 2 days of ischemia (Online Figure I).…”