Abstract 250: Endothelial Cell Endothelin (ET-1) Production is Enhanced with Increasing NaCl Concentration.
It has recently been demonstrated that increasing salt intake results in an accumulation of sodium within the interstitium of the skin of normal rats, which leads to an immune response that is necessary to maintain normal blood pressure. ET-1 mediates increased inflammation in several models of hypertension and is increased in response to high salt intake. However, it is unknown if ET-1 production is increased by endothelial cells in response to increasing NaCl concentration. Therefore, we hypothesized that increasing the media NaCl concentration will lead to an increase in ET-1 production by human umbilical venous endothelial cells (HUVECs). Exposure of HUVECs for 2 hours to a 40 mosm increase in NaCl results in a significant increase in ET-1 mRNA (1.65±0.14 fold increase vs. control; n=3, p<0.05). This increase in Na+ concentration is similar to that observed in the interstitium of the skin of rats placed on a high NaCl diet. Furthermore, exposure to +40 mosm of mannitol, an effective osmolyte, or urea, an ineffective osmolyte, had no effect on ET-1 mRNA (1.1 ± 0.04 fold change and 1.07 ± .08 fold change vs. control, respectively; n=3, p<0.05) suggesting that a direct effect of NaCl, not osmolality, is responsible for the increase in ET-1 mRNA. Moreover, +40 mosm of sodium acetate (NaAc) or choline chloride (ChCl) resulted in an increase in ET-1 mRNA very similar to that seen by increasing NaCl (1.74±0.14 (NaCl), 1.54±0.05 (NaAc), and 1.59±0.03 (ChCl) fold change vs. control, n=3, p<0.05), suggesting that either the Na or Cl ion increases ET-1 expression. These data demonstrate that vascular endothelial cells express ET-1 in response to increases in NaCl concentration, and may be important in mediating the extrarenal inflammatory response to a high salt diet.
- © 2012 by American Heart Association, Inc.