The surface of endothelial cells is covered by a glycocalyx which forms the endothelial surface layer (ESL) by binding ions and plasma proteins. The ESL plays an important role in the flow dependent regulation of blood pressure by sensing the blood flow-induced fluid shear stress. There are indications that excessive plasma sodium concentrations stiffen the ESL and impair vasorelaxation. We hypothesize that the stiffness of the ESL is an important factor in the regulation of blood pressure. It was shown that some polyphenols increase the endothelial NO synthesis and exert cardioprotective and vasodilating properties. By using simultaneous atomic force - epifluorescence microscopy we measured the effect of a polyphenolic compound (WS 1442, herbal extract fromCrataegusspp.) on the mechanics of the ESL ofex vivomurine aortae. Additionally, the contribution of the ESL to endothelial barrier resistance for sodium and the impact of WS 1442 on this barrier resistance were examinedin vitro. Our data reveal that polyphenols extracted from hawthorn lead within minutes to a decrease in ESL stiffness by about 30% and an increase in ESL thickness by about 22%. Furthermore we can show that the ESL contributes about 11% to the total endothelial barrier resistance for sodium. Application of polyphenols leads to an increase in ESL barrier resistance for sodium by about 45%. This mechanism may explain some of the vasoprotective properties of polyphenols and improve the understanding of functions of the ESL.