Science's STKE (Signal Transduction Knowledge Environment) discussed the paper of Oberleithner et al. in the editor's choice section in October 2007.

	Human endothelial cells from the umbilical cord vein, AFM. First high resolution image of the endothelial cell surface performed in fluid.

Ingestion of large amounts of salt in the diet has been associated with increased blood pressure and harmful cardiovascular effects, but precisely how salt influences blood pressure is not clear. Oberleithner et al. describe experiments showing a direct effect of sodium on the physical stiffness of endothelial cells. The authors tested the effects on endothelial cells of small changes in sodium concentration (from about 130 to 150 mm) within a range that corresponds to that observed in humans ingesting a high-salt diet. They monitored changes in stiffness of cultured human endothelial cells by atomic force microscopy. Increases in the concentration of sodium increased stiffness of the endothelial cells within minutes, provided that the cells also were exposed to physiological concentrations of the hormone aldosterone. The increase in stiffness was inhibited in cells exposed to amilioride, an inhibitor of epithelial sodium channels.

The authors applied simulated shear stress to the cells by shaking the culture flasks, a treatment expected to enhance accumulation of nitric oxide. Under these conditions, increased sodium concentration decreased the nitrite concentration in the culture medium. It remains unclear how the cells are sensing the extracellular concentration of sodium (a change in osmolality was prevented in the experiments by addition of mannitol).

The authors propose that swelling of endothelial cells in response to relatively small increases in sodium concentration in the blood might have important effects on blood pressure. Endothelial cells sense mechanical stress, and their normal response of activating nitric oxide synthase appears to be blunted when the cells swell and stiffen after exposure to higher sodium concentrations. This could lead to increases in total vascular resistance and contributed to the deleterious effects of hypertension.

Citation: L. B. Ray, Endothelial Cells as Salt Sensors. Sci. STKE, 16 October 2007; Vol. 2007, Issue 408, p. tw372; [DOI: 10.1126/stke.4082007tw372]

Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

The two images, obtained with atomic force microscopy, show living endothelial cells exposed to either low sodium (upper left) or high sodium (lower right). Due to the increased stiffness, induced by high sodium, cells are less flattened by the scanning tip and thus appear more prominent.

Dietary salt plays a major role in the regulation of blood pressure, and the mineralocorticoid hormone aldosterone controls salt homeostasis and extracellular volume. Recent observations suggest that a small increase in plasma sodium concentration may contribute to the pressor response of dietary salt. Because endothelial cells are (i) sensitive to aldosterone, (ii) in physical contact with plasma sodium, and (iii) crucial regulators of vascular tone, we tested whether acute changes in plasma sodium concentration, within the physiological range, can alter the physical properties of endothelial cells. The tip of an atomic force microscope was used as a nanosensor to measure stiffness of living endothelial cells incubated for 3 days in a culture medium containing aldosterone at a physiological concentration (0.45 nM). Endothelial cell stiffness was unaffected by acute changes in sodium concentration <135 mM but rose steeply between 135 and 145 mM. The increase in stiffness occurred within minutes. Lack of aldosterone in the culture medium or treatment with the epithelial sodium channel inhibitor amiloride prevented this response. Nitric oxide formation was found down-regulated in cells cultured in aldosterone-containing high sodium medium. The results suggest that changes in plasma sodium concentration per se may affect endothelial function and thus control vascular tone.

Keywords: atomic force microscopy cell stiffness endothelial dysfunction eplerenone

Source

Plasma sodium stiffens vascular endothelium and reduces nitric oxide release

Hans Oberleithner, Christoph Riethmueller, Hermann Schillers, Graham A. MacGregor, Hugh E. de Wardener, and Martin Hausberg,

PNAS October 9, 2007, vol. 104, no. 41, 16281-16286,

www.pnas.org, cgi doi 10.1073 pnas.0707791104