Sodium renders endothelial cells sticky for red blood cells

Abstract

Negative charges in the glycocalyx of red blood cells (RBC) and vascular endothelial cells (EC) facilitate frictionless blood flow through blood vessels. Na+ selectively shields these charges controlling surface electronegativity. The question was addressed whether the ambient Na+ concentration controls RBC-EC interaction. Using atomic force microscopy (AFM) adhesion forces between RBC and endothelial glycocalyx were quantified. A single RBC, mounted on an AFM cantilever, was brought in physical contact with the endothelial surface and then pulled off. Adhesion forces were quantified (i) after enzymatic removal of negative charges in the glycocalyx, (ii) under different ambient Na+ and (iii) after applying the intracellular aldosterone receptor antagonist spironolactone. Removal of negative surface charges increases RBC-EC interaction forces. A stepwise increase of ambient Na+ from 133 to 140 mM does not affect them. However, beyond 140 mM Na+ adhesion forces increase sharply (10% increase of adhesion force per 1 mM increase of Na+). Spironolactone prevents this response. It is concluded that negative charges reduce adhesion between RBC and EC. Ambient Na+ concentration determines the availability of free negative charges. Na+ concentrations in the low physiological range (below 140 mM) allow sufficient amounts of vacant negative charges so that adhesion of RBC to the endothelial surface is small. In contrast, Na+ in the high physiological range (beyond 140 mM) saturates the remaining negative surface charges thus increasing adhesion. Aldosterone receptor blockade by spironolactone prevents Na+ induced RBC adhesion to the endothelial glycocalyx. Extrapolation of in vitro experiments to in vivo conditions leads to the hypothesis that high sodium intake is likely to increase the incidence of thrombotic events.

Translational research into vascular wall function: regulatory effects of systemic and specific factors

“…Since a vast the glycocalyx) and on circulating blood components e.g., red blood cells facilitates frictionless blood flow. Removal of the surface negative charge (as a result of enzyme reaction) enhances red blood cell adhesion to endothelial cells [34]. A similar effect is produced by sodium cation.…”

“…At Na + concentrations <140 мМ the number of vacant negative charges remains sufficient to maintain adhesion of red blood cells to endothelial lining at a low level. Sodium renders endothelium sticky for red blood cells [34]. Storage of plasma Na + in the glycocalyx (with partial neutralization of negative surface charge) allows one to divide glycocalyx into "good" which has a capacity for Na + accumulation to maintain sufficient negative charge at normal plasma Na + concentration and "bad" when the loss of negative charge increases adverse interactions between endothelium and red blood cells [35].…”

Erythrocyte Sodium Sensitivity and Eryptosis in Chronic Hemodialysis Patients

“…found that the RBC cell surface properties could be partially restored through the dialysis treatment, especially in those individuals with high serum sodium concentrations before the treatment [47]. It has been shown in vitro that sodium concentrations higher than 140 mmol/L impair the glycocalyx and increase adherence of erythrocytes to endothelial cells [48]. In our population the ESS was not significantly altered through the HD treatment itself, possibly due to preHD serum sodium concentrations (137.7 ± 2.4 mmol/L) close to the prescribed dialysate sodium of 137 mmol/L.…”

Salt Sensitivity Determined From Capillary Blood

“…For example, application of polyphenolic compounds in vitro [12] and in vivo [16] can influence SS. Also elevated concentrations of plasma sodium can gradually destroy the charged surface layers of endothelium and RBC as recently demonstrated [8,31,32]. Furthermore, SS changes in inflammatory diseases/atherothrombotic processes are likely to occur since endothelial surface layers are known to lose their negative charges under such conditions [33][34][35].…”