High cellular elasticity of vascular endothelium is a prerequisite for adequate function of blood vessels. Endothelial cells are usually exposed to mechanical forces such as fluid drag und pulse pressure which control nitric oxide release and other regulatory mechanisms. By means of nanotechniques, based on atomic force microscopy (AFM) and fluorescence techniques, based on nanocrystals (Q-dot labeled antibodies), we developed a functional concept of endothelial cell mechanics. Major roles in this concept (1, 2) play the mineralocorticoid hormone aldosterone, the concentration of extracellular ions and the expression of epithelial sodium channels (ENaCs) in endothelial cells. It was found that the number of ENaCs in the apical plasma membrane correlates positively with mechanical cell stiffness and negatively with nitric oxide release. In other words, ENaC expression determines cellular elasticity and thus endothelial function (3). This hypothesis has been tested in different ways and in different endothelial cell models. ENaC is found upregulated by high sodium/aldosterone exposure using primary cultures, endothelial cells lines and ex vivo artery preparations. Furthermore, endothelial cells of ex vivo arteries excised from Liddle-mice (genetic gain-of-function mutation of ENaC) are stiffer as compared to the wildtype. Down-regulation of ENaC by si-RNA experiments in vitro leads to endothelial cell softening. Experiments indicate that there is a direct link between ENaC and cortical actin which determines endothelial stiffness and NO release. Recent advances in the application of the AFM technique allow a differentiation between the bulk cell stiffness, the stiffness of the cell membrane including the cortical actin web and the stiffness of the glycocalyx on the cell surface. This functional sectioning of the different layers should allow to unravelling the physiological and pathophysiological mechanisms underlying the regulation of tissue perfusion and blood pressure.
1. Oberleithner H, Callies C, Kusche-Vihrog K, Schillers H, Shahin V, Riethmuller C, MacGregor GA, & de Wardener HE (2009) Potassium softens vascular endothelium and increases nitric oxide release. Proc Natl Acad Sci U S A 106:2829-2834.
2. Oberleithner H, Riethmuller C, Schillers H, MacGregor GA, de Wardener HE, & Hausberg M (2007) Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc Natl Acad Sci U S A 104:16281-16286.
3. Kusche-Vihrog K, Callies C, Fels J, & Oberleithner H (2010) The epithelial sodium channel (ENaC): Mediator of the aldosterone response in the vascular endothelium? Steroids 75:544-549.