Vascular endothelin (ET‐1) mediates skin Na+ storage in response to chronic increases in salt intake (860.13)

Abstract

We have recently implicated extrarenal vascular ET‐1 in the body’s integrated response to a chronic high salt intake by mediating storage of Na+ within the skin. We hypothesize that upregulation of vascular ET‐1 in response to a high salt diet leads to the recruitment of macrophages and lymphocytes to the interstitium of the skin, which promote lymph hyperplasia, all of which provide a buffer for extracellular Na+ homeostasis. In the present study, we determined if vascular endothelial cell ET‐1 knockout mice (VEET KO) have reduced vascular cell adhesion molecule expression and increased skin Na+ storage in response to a high salt diet. After 2 weeks of a high NaCl (4%) diet, VEET KO mice have higher total skin Na/water ratio than floxed controls (0.112±0.007 vs. 0.096±0.003 mmol/ml respectively). Floxed control mice have elevated ET‐1 mRNA in the aorta compared to animals on low salt (1.38±0.21 vs. 1.05±0.14 fold change respectively, n=6), a response that was completely blunted in VEET KO mice (1.07±0.12 vs. 1.05±0.16 fold change, n=5). There was no change in vascular cell adhesion molecule‐1 between groups. These data support our hypothesis that vascular endothelial derived ET‐1 plays a critical role in mediating skin storage of Na+ in response to a high salt intake.Grant Funding Source: Supported by NHLBI and AHA