Acclimation to a High-Salt Diet Is Sex Dependent

Academic Article


  • BACKGROUND: Premenopausal women are less likely to develop hypertension and salt-related complications than are men, yet the impact of sex on mechanisms regulating Na+ homeostasis during dietary salt challenges is poorly defined. Here, we determined whether female rats have a more efficient capacity to acclimate to increased dietary salt intake challenge. METHODS AND RESULTS: Age-matched male and female Sprague Dawley rats maintained on a normal-salt (NS) diet (0.49% NaCl) were challenged with a 5-day high-salt diet (4.0% NaCl). We assessed serum, urinary, skin, and muscle electrolytes; total body water; and kidney Na+ transporters during the NS and high-salt diet phases. During the 5-day high-salt challenge, natriuresis increased more rapidly in females, whereas serum Na+ and body water concentration increased only in males. To determine if females are primed to handle changes in dietary salt, we asked the question whether the renal endothelin-1 natriuretic system is more active in female rats, compared with males. During the NS diet, female rats had a higher urinary endothelin-1 excretion rate than males. Moreover, Ingenuity Pathway Analysis of RNA sequencing data identified the enrich-ment of endothelin signaling pathway transcripts in the inner medulla of kidneys from NS-fed female rats compared with male counterparts. Notably, in human subjects who consumed an Na+-controlled diet (3314– 3668 mg/day) for 3 days, women had a higher urinary endothelin-1 excretion rate than men, consistent with our findings in NS-fed rats. CONCLUSIONS: These results suggest that female sex confers a greater ability to maintain Na+ homeostasis during acclimation to dietary Na+ challenges and indicate that the intrarenal endothelin-1 natriuretic pathway is enhanced in women.
  • Digital Object Identifier (doi)

    Author List

  • Gohar EY; De Miguel C; Obi IE; Daugherty EM; Hyndman KA; Becker BK; Jin C; Sedaka R; Johnston JG; Liu P
  • Volume

  • 11
  • Issue

  • 5