Endothelin-1 as a master regulator of whole-body Na+ homeostasis

Joshua S. Speed, J. Brett Heimlich, Kelly A. Hyndman, Brandon M. Fox, Vivek Patel, Masashi Yanagisawa, Jennifer S. Pollock, Jens M. Titze, David M. Pollock

Research output: Contribution to journalArticle

14 Citations (Scopus)

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+:H2O in HS fed mice (0.119 ± 0.005 mM vs. 0.127 ± 0.007 mM; LS vs. HS); however, skin Na+:H2O 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 ± 0.9 pg/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+:H2O (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 productionin response to HS intake is mediated by increased extracellular osmolarity and plays a critical role in regulating skin storage of Na+.

Original languageEnglish (US)
Pages (from-to)4937-4944
Number of pages8
JournalFASEB Journal
Volume29
Issue number12
DOIs
StatePublished - Dec 1 2015

Fingerprint

Endothelin-1
Homeostasis
Skin
Osmolar Concentration
Endothelial cells
Blood Vessels
Endothelial Cells
Knockout Mice
Animals
Tissue
Plasmas
Endothelin A Receptors
Inbred C57BL Mouse
Salts
Messenger RNA
Peptides

Keywords

  • Endothelium
  • Inflammation
  • Skin
  • Vascular

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Speed, J. S., Heimlich, J. B., Hyndman, K. A., Fox, B. M., Patel, V., Yanagisawa, M., ... Pollock, D. M. (2015). Endothelin-1 as a master regulator of whole-body Na+ homeostasis. FASEB Journal, 29(12), 4937-4944. https://doi.org/10.1096/fj.15-276584

Endothelin-1 as a master regulator of whole-body Na+ homeostasis. / 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.

In: FASEB Journal, Vol. 29, No. 12, 01.12.2015, p. 4937-4944.

Research output: Contribution to journalArticle

Speed, JS, Heimlich, JB, Hyndman, KA, Fox, BM, Patel, V, Yanagisawa, M, Pollock, JS, Titze, JM & Pollock, DM 2015, 'Endothelin-1 as a master regulator of whole-body Na+ homeostasis', FASEB Journal, vol. 29, no. 12, pp. 4937-4944. https://doi.org/10.1096/fj.15-276584
Speed JS, Heimlich JB, Hyndman KA, Fox BM, Patel V, Yanagisawa M et al. Endothelin-1 as a master regulator of whole-body Na+ homeostasis. FASEB Journal. 2015 Dec 1;29(12):4937-4944. https://doi.org/10.1096/fj.15-276584
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. / Endothelin-1 as a master regulator of whole-body Na+ homeostasis. In: FASEB Journal. 2015 ; Vol. 29, No. 12. pp. 4937-4944.
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