Endothelin mediates sex-differences in acclimation to high salt diet in rats.

Introduction: Current understanding of sodium (Na ⁺ ) handling is based on studies done primarily in males. Contrary to the gradual increase in high salt (HS) induced natriuresis over 3-5 days in males, female Sprague Dawley (SD) rats have a robust natriuresis after 1 day of HS. Renal endothelin-1 (ET-1) signaling, through ET receptor A and B, is an important natriuretic pathway and was implicated in our previous dietary salt acclimation studies, however, the contribution of ET receptors to sex-differences in acclimation to dietary Na ⁺ challenges has yet to be clarified. We hypothesized that ET receptors mediate the augmented natriuretic capacity of female rats in response to a HS diet.
Methods: To test our hypothesis, male and female SD rats were implanted with telemeters and randomly assigned to treatment with A-182086, a dual ET _A and ET _B receptor antagonist, or control. 24-h urine samples were collected and assessed for electrolytes and ET-1. Studies were performed on a normal salt (NS, 0.3% NaCl) diet and after challenging rats with HS (4% NaCl) diet for 1 day.
Results: We found that A-182086 increased blood pressure in male and female SD rats fed either diet. Importantly, A-182086 eliminated sex-differences in natriuresis on NS and HS. In particular, A-182086 promotes HS-induced natriuresis in male rats rather than attenuating the natriuretic capacity of females. Further, the sex-difference in urinary ET-1 excretion in NS-fed rats was eliminated by A-182086.
Conclusion: In conclusion, ET receptors are crucial for mediating sex-difference in the natriuretic capacity primarily through their actions in male rats.
(© 2023. Society for Women's Health Research and BioMed Central Ltd.)