Acclimation to a High‐Salt Diet Is Sex Dependent

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...

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Main Authors: Eman Y. Gohar, Carmen De Miguel, Ijeoma E. Obi, Elizabeth M. Daugherty, Kelly A. Hyndman, Bryan K. Becker, Chunhua Jin, Randee Sedaka, Jermaine G. Johnston, Pengyuan Liu, Joshua S. Speed, Tanecia Mitchell, Alison J. Kriegel, Jennifer S. Pollock, David M. Pollock
Format: Article
Language:English
Published: Wiley 2022-03-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
Subjects:
Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.120.020450
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author Eman Y. Gohar
Carmen De Miguel
Ijeoma E. Obi
Elizabeth M. Daugherty
Kelly A. Hyndman
Bryan K. Becker
Chunhua Jin
Randee Sedaka
Jermaine G. Johnston
Pengyuan Liu
Joshua S. Speed
Tanecia Mitchell
Alison J. Kriegel
Jennifer S. Pollock
David M. Pollock
author_facet Eman Y. Gohar
Carmen De Miguel
Ijeoma E. Obi
Elizabeth M. Daugherty
Kelly A. Hyndman
Bryan K. Becker
Chunhua Jin
Randee Sedaka
Jermaine G. Johnston
Pengyuan Liu
Joshua S. Speed
Tanecia Mitchell
Alison J. Kriegel
Jennifer S. Pollock
David M. Pollock
author_sort Eman Y. Gohar
collection DOAJ
description 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 enrichment 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.
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spelling doaj.art-0cb3e71087914936a984fb5185dc2cdf2023-07-06T05:53:20ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802022-03-0111510.1161/JAHA.120.020450Acclimation to a High‐Salt Diet Is Sex DependentEman Y. Gohar0Carmen De Miguel1Ijeoma E. Obi2Elizabeth M. Daugherty3Kelly A. Hyndman4Bryan K. Becker5Chunhua Jin6Randee Sedaka7Jermaine G. Johnston8Pengyuan Liu9Joshua S. Speed10Tanecia Mitchell11Alison J. Kriegel12Jennifer S. Pollock13David M. Pollock14Section of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALDepartment of Physiology Medical College of Wisconsin Milwaukee WIDepartment of Physiology University of Mississippi Medical Center Jackson MSDepartment of Urology University of Alabama at Birmingham ALDepartment of Physiology Medical College of Wisconsin Milwaukee WISection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALSection of Cardio‐Renal Physiology & Medicine Division of Nephrology Department of Medicine University of Alabama at Birmingham ALBackground 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 enrichment 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.https://www.ahajournals.org/doi/10.1161/JAHA.120.020450endothelin‐1natriuresisnitric oxidesex differencessodium
spellingShingle Eman Y. Gohar
Carmen De Miguel
Ijeoma E. Obi
Elizabeth M. Daugherty
Kelly A. Hyndman
Bryan K. Becker
Chunhua Jin
Randee Sedaka
Jermaine G. Johnston
Pengyuan Liu
Joshua S. Speed
Tanecia Mitchell
Alison J. Kriegel
Jennifer S. Pollock
David M. Pollock
Acclimation to a High‐Salt Diet Is Sex Dependent
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
endothelin‐1
natriuresis
nitric oxide
sex differences
sodium
title Acclimation to a High‐Salt Diet Is Sex Dependent
title_full Acclimation to a High‐Salt Diet Is Sex Dependent
title_fullStr Acclimation to a High‐Salt Diet Is Sex Dependent
title_full_unstemmed Acclimation to a High‐Salt Diet Is Sex Dependent
title_short Acclimation to a High‐Salt Diet Is Sex Dependent
title_sort acclimation to a high salt diet is sex dependent
topic endothelin‐1
natriuresis
nitric oxide
sex differences
sodium
url https://www.ahajournals.org/doi/10.1161/JAHA.120.020450
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