Differential action of steroid hormones on human endothelium

• DOI: 10.1242/jcs.02886
• Publication Date: 2006-04-24T16:29:27Z
• Authors: Hans Oberleithner; Christoph Riethmu...; Thomas Ludwig; Victor Shahin; Christian Stock; Albrecht Schwab; Martin Hausberg; Kristina Kusche; Hermann Schillers
• Keywords: 0301 basic medicine; 0303 health sciences; Cell Membrane; Cell Polarity; Endothelial Cells; Spironolactone; Microscopy, Atomic Force; Dexamethasone; Elasticity; Cell Line; 3. Good health; Mifepristone; 03 medical and health sciences; Hormone Antagonists; Electric Impedance; Humans; Aldosterone; Glucocorticoids; Mineralocorticoid Receptor Antagonists

The action of glucocorticoids on vascular permeability is well established. However, little is known about the action of mineralocorticoids on the structure and function of blood vessels. As endothelial cells are targets for both glucocorticoids and mineralocorticoids, we exposed human umbilical vein endothelial cells to both types of steroids. Aldosterone (mineralocorticoid) and dexamethasone (glucocorticoid) were applied for 3 days in culture before measurements of transendothelial ion and macromolecule permeability, apical cell surface and cell stiffness were taken. Transendothelial ion permeability was measured with electrical cell impedance sensing, macromolecule permeability with fluorescence-labeled dextran and apical cell membrane surface by three-dimensional AFM imaging. Cell stiffness was measured using the AFM scanning tip as a mechanical nanosensor. We found that aldosterone increased both apical cell surface and apical cell stiffness significantly, while transendothelial permeability remained unaffected. By contrast, dexamethasone significantly decreased ion and macromolecule permeability, while apical cell surface and cell stiffness did not change. Specific receptor antagonists for dexamethasone (RU486) and aldosterone (spironolactone) prevented the observed responses. We conclude that glucocorticoids strengthen cell-to-cell contacts (`peripheral action'), whereas mineralocorticoids enlarge and stiffen cells (`central action'). This could explain the dexamethasone-mediated retention of fluid in the vascular system, and endothelial dysfunction in states of hyperaldosteronism.