Sodium intake and biological sex influence urinary endothelin-1 in salt-resistantadults: a pilot study
Date
2025-08-19
Journal Title
Journal ISSN
Volume Title
Publisher
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Abstract
Hypertension is more prevalent in males than age-matched premenopausal females. Average sodium intake in the United States ishigher than recommended and is a risk factor for developing hypertension. Sex differences in renal sodium homeostasis may underliesex differences in hypertension prevalence. For example, renal endothelin-1 (ET-1) plays a key role in the maintenance of blood pres-sure and sodium homeostasis. Previous rodent studies demonstrate that females excrete higher urinary ET-1 compared with males,and increasing dietary sodium promotes urinary ET-1 excretion only in male rats. However, the impact of sex on sodium and renal ET-1 signaling in humans is unclear. Therefore, we aimed to determine whether the renal ET-1 system responds differently to salt loadingin male and female human research participants. To test our hypothesis, normotensive salt-resistant male and female participantswere administered a low (1 g/day), recommended (2.3 g/day), and high (7 g/day) sodium diet for 10 days each in random order. The24-h urine samples were collected and assessed for sodium and ET-1. Following increased dietary sodium, both males and femalesincreased urinary sodium excretion (diet: P < 0.001). Following increased dietary sodium, participants exhibited an increased urinaryET-1 excretion (diet: P ¼ 0.038). Interestingly, post hoc testing revealed that only females displayed an increase in ET-1 excretion (rec-ommended vs. high sodium, P ¼ 0.009). Overall, the current human study provides novel insights into potential sex-specific modula-tion of ET-1 and renal responses to dietary sodium. Further investigations are warranted to understand the underlying molecularmechanisms driving sex-related differences in renal ET-1 signaling and sodium handling.
Description
This article was originally published in American Journal of Physiology - Regulatory, Integrative and Comparative Physiology. The version of record is available at: https://doi.org/10.1152/ajpregu.00119.2025
0363-6119/25 Copyright © 2025 The Authors. Licensed under Creative Commons Attribution CC-BY 4.0. https://creativecommons.org/licenses/by/4.0/
Published by the American Physiological Society.
Keywords
blood pressure, natriuresis, salt, salt-resistance, sex
Citation
Nasci, Victoria L., Jazmine I. Benjamin, Rebecca C. Fetter, et al. “Sodium Intake and Biological Sex Influence Urinary Endothelin-1 in Salt-Resistant Adults: A Pilot Study.” American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 329, no. 3 (2025): R487–94. https://doi.org/10.1152/ajpregu.00119.2025.