Diurnal pattern in skin Na+ and water content is associated with salt-sensitive hypertension in ETB receptor-deficient rats

Am J Physiol Regul Integr Comp Physiol. 2018 Apr 1;314(4):R544-R551. doi: 10.1152/ajpregu.00312.2017. Epub 2017 Dec 13.

Abstract

Impairment in the ability of the skin to properly store Na+ nonosmotically (without water) has recently been hypothesized as contributing to salt-sensitive hypertension. Our laboratory has shown that endothelial production of endothelin-1 (ET-1) is crucial to skin Na+ handling. Furthermore, it is well established that loss of endothelin type B receptor (ETB) receptor function impairs Na+ excretion by the kidney. Thus we hypothesized that rats lacking functional ETB receptors (ETB-def) will have a reduced capacity of the skin to store Na+ during chronic high-salt (HS) intake. We observed that ETB-def rats exhibited salt-sensitive hypertension with an approximate doubling in the diurnal amplitude of mean arterial pressure compared with genetic control rats on a HS diet. Two weeks of HS diet significantly increased skin Na+ content relative to water; however, there was no significant difference between control and ETB-def rats. Interestingly, HS intake led to a 19% increase in skin Na+ and 16% increase in water content (relative to dry wt.) during the active phase (zeitgeber time 16) versus inactive phase (zeitgeber time 4, P < 0.05) in ETB-def rats. There was no significant circadian variation in total skin Na+ or water content of control rats fed normal or HS. These data indicate that ETB receptors have little influence on the ability to store Na+ nonosmotically in the skin during long-term HS intake but, rather, appear to regulate diurnal rhythms in skin Na+ content and circadian blood pressure rhythms associated with a HS diet.

Keywords: circadian rhythm; endothelin; salt; skin; sodium.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure*
  • Body Water / metabolism*
  • Circadian Rhythm*
  • Disease Models, Animal
  • Endothelin-1 / metabolism
  • Hypertension / genetics
  • Hypertension / metabolism*
  • Hypertension / physiopathology
  • Male
  • Rats, Transgenic
  • Receptor, Endothelin B / deficiency*
  • Receptor, Endothelin B / genetics
  • Signal Transduction
  • Skin / metabolism*
  • Sodium Chloride, Dietary / metabolism*
  • Time Factors

Substances

  • Endothelin-1
  • Receptor, Endothelin B
  • Sodium Chloride, Dietary
  • ednrb protein, rat