Endothelin‐1 as a master regulator of whole‐body Na+ homeostasis. Issue 12 (12th August 2015)

• Record Type: Journal Article
• Authors: Speed, Joshua S.; Heimlich, J. Brett; Hyndman, Kelly A.; Fox, Brandon M.; Patel, Vivek; Yanagisawa, Masashi; Pollock, Jennifer S.; Titze, Jens M.; Pollock, David M.
• Is Part Of: FASEB journal. Volume 29:Issue 12(2015)
• Page Start: 4937
• Page End: 4944
• Publication Date: 2015-08-12
• Subjects: skin -- endothelium -- vascular -- inflammation; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.15-276584
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: The current study was designed to determine whether vascular endothelial‐derived endothelin‐1 (ET‐1) is important for skin Na + buffering. In control mice (C57BL/6J), plasma Na + and osmolarity were significantly elevated in animals on high‐ vs. low‐salt (HS and LS, respectively) intake. The increased plasma Na + and osmolarity were associated with increased ET‐1 mRNA in vascular tissue. There was no detectable difference in skin Na + :H2 O in HS fed mice (0.119 ± 0.005 mM vs. 0.127 ± 0.007 mM; LS vs. HS); however, skin Na + :H2 O was significantly increased by blockade of the endothelin type A receptor with ABT‐627 (0.116 ± 0.006 mM vs. 0.137 ± 0.007 mM; LS vs. HS; half‐maximal inhibitory concentration, 0.055 nM). ET‐1 peptide content in skin tissue was increased in floxed control animals on HS (85.9 ± 0.9pg/mg vs. 106.4 ± 6.8 pg/mg; P < 0.05), but not in vascular endothelial cell endothelin‐1 knockout (VEET KO) mice (76.4 ± 5.7 pg/mg vs. 65.7 ± 7.9 pg/mg; LS vs. HS). VEET KO mice also had a significantly elevated skin Na + :H2 O (0.113 ± 0.007 mM vs. 0.137 ± 0.005 mM; LS vs. HS; P < 0.05). Finally, ET‐1 production was elevated in response to increasing extracellular osmolarity in cultured human endothelial cells. These data support the hypothesis that increased extrarenal vascular ET‐1 production in response to HS intake is mediated by increased extracellular osmolarity and plays a critical role in regulating skin storage of Na + .—Speed, J. S., Heimlich, J. B., Hyndman, K. A., Fox, B. M., Patel, V., Yanagisawa, M., Pollock, J. S., Titze, J. M., Pollock, D. M. Endothelin‐1 as a master regulator of whole‐body Na + homeostasis. FASEB J. 29, 4937–4944 (2015). www.fasebj.org