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Endothelial cell derived endothelin‐1 (ET‐1) regulates skin Na + storage: evidence for sex differences
Author(s) -
Speed Joshua,
Pollock David
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.811.9
Subject(s) - endocrinology , medicine , hyperplasia , lymph , chemistry , pathology
The skin stores sodium in response to chronic high salt intake providing a buffer for extracellular fluid volume through macrophage recruitment and lymph hyperplasia. ET‐1 is increased in response to high salt intake and promotes pro‐inflammatory and hyperplastic effects, although its role in skin Na + storage is unknown. Therefore, the current study was designed to determine if vascular endothelial derived ET‐1 is important to the skin buffering capacity and if sex differences exist in this response. After 2 weeks of either low (LS, .02%) or high (HS, 4%) NaCl diet, floxed control mice had a slight, but not statistically significant increase in skin Na + concentration. Na + content was similar in both males and females. This response was significantly exacerbated in VEET KO mice. Furthermore, tissue ET‐1 peptide levels were significantly higher in response to HS in the ear, a highly vascularized skin tissue, of male floxed mice (85.9±0.9 ng/mg LS vs. 106.4± 6.8 ng/mg HS, p<0.05). Male VEET KO mice had significantly lower ET‐1 in the ear compared to floxed controls with no difference between LS and HS (76.4±5.7 ng/mg LS vs. 65.7±7.9 ng/mg). In contrast, female mice have elevated ET‐1 in the ear compared to males. Both floxed and VEET KO female mice have a similar increase in ear ET‐1 in response to HS (floxed; LS vs. HS respectively, 113±13 vs. 141±23 ng/mg; VEET KO; LS vs. HS respectively, 112.0±16.2 LS vs. 156.3±24.1 ng/mg). These data support the hypothesis that vascular endothelial derived ET‐1 plays a critical role in mediating skin storage of Na + in response to a high salt intake. We also suggest that female mice have another source of ET‐1 within the skin interstitium that may contribute to a greater ability to store and clear Na + in the skin.