Editors' ChoicePhysiology

Endothelial Cells as Salt Sensors

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Science's STKE  16 Oct 2007:
Vol. 2007, Issue 408, pp. tw372
DOI: 10.1126/stke.4082007tw372

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.

H. Oberleithner, C. Riethmüller, H. Schillers, G. A. MacGregor, H. E. de Wardener, M. Hausberg, Plasma sodium stiffens vascular endothelium and reduces nitric oxide release. Proc. Natl. Acad. Sci. U.S.A. 104, 16281-16286 (2007). [Abstract] [Full Text]