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

Speed JS, Heimlich JB, Hyndman KA, Fox BM, Patel V, Yanagisawa M, Pollock JS, Titze J, Pollock DM (2015)

Publication Type: Journal article

Publication year: 2015

Journal

The FASEB Journal Federation of American Society of Experimental Biology (FASEB)

Book Volume: 29

Pages Range: 4937-44

Journal Issue: 12

DOI: 10.1096/fj.15-276584

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 production in response to HS intake is mediated by increased extracellular osmolarity and plays a critical role in regulating skin storage of Na(+).

Authors with CRIS profile

Jens Titze Department of Medicine 4 – Nephrology and Hypertension

Involved external institutions

University of Alabama at Birmingham (UAB) US United States (USA) (US) University of Tsukuba / 筑波大学 JP Japan (JP) Augusta University US United States (USA) (US)

How to cite

APA:

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. The FASEB Journal, 29(12), 4937-44. https://doi.org/10.1096/fj.15-276584

MLA:

Speed, Joshua S., et al. "Endothelin-1 as a master regulator of whole-body Na+ homeostasis." The FASEB Journal 29.12 (2015): 4937-44.

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