mTORC1 Deficiency Modifies Volume Homeostatic Responses to Dietary Sodium in a Sex-Specific Manner.
Aldosterone
/ metabolism
Animals
Blood Pressure
/ drug effects
Female
Homeostasis
/ drug effects
Hypertension
/ physiopathology
Kidney
/ metabolism
Male
Mechanistic Target of Rapamycin Complex 1
/ deficiency
Myocardium
/ metabolism
Regulatory-Associated Protein of mTOR
/ deficiency
Sex Factors
Signal Transduction
/ drug effects
Sodium, Dietary
/ pharmacology
Time Factors
Raptor
aldosterone
cardiovascular disease
mTOR
salt intake
Journal
Endocrinology
ISSN: 1945-7170
Titre abrégé: Endocrinology
Pays: United States
ID NLM: 0375040
Informations de publication
Date de publication:
01 05 2020
01 05 2020
Historique:
received:
27
09
2019
accepted:
06
03
2020
pubmed:
11
3
2020
medline:
5
1
2021
entrez:
11
3
2020
Statut:
ppublish
Résumé
The mechanistic target of the rapamycin (mTOR) pathway plays a role in features common to both excess salt/aldosterone and cardiovascular/renal diseases. Dietary sodium can upregulate mTORC1 signaling in cardiac and renal tissue, and the inhibition of mTOR can prevent aldosterone-associated, salt-induced hypertension. The impact of sex and age on mTOR's role in volume homeostasis and the regulation of aldosterone secretion is largely unknown. We hypothesize that both age and sex modify mTOR's interaction with volume homeostatic mechanisms. The activity of 3 volume homeostatic mechanisms-cardiovascular, renal, and hormonal (aldosterone [sodium retaining] and brain natriuretic peptide [BNP; sodium losing])-were assessed in mTORC1 deficient (Raptor+/-) and wild-type male and female littermates at 2 different ages. The mice were volume stressed by being given a liberal salt (LibS) diet. Raptor+/-mice of both sexes when they aged: (1) reduced their blood pressure, (2) increased left ventricular internal diameter during diastole, (3) decreased renal blood flow, and (4) increased mineralocorticoid receptor expression. Aldosterone levels did not differ by sex in young Raptor+/- mice. However, as they aged, compared to their littermates, aldosterone decreased in males but increased in females. Finally, given the level of Na+ intake, BNP was inappropriately suppressed, but only in Raptor+/- males. These data indicate that Raptor+/- mice, when stressed with a LibS diet, display inappropriate volume homeostatic responses, particularly with aging, and the mechanisms altered, differing by sex.
Identifiants
pubmed: 32154868
pii: 5802448
doi: 10.1210/endocr/bqaa041
pmc: PMC7391217
pii:
doi:
Substances chimiques
Regulatory-Associated Protein of mTOR
0
Rptor protein, mouse
0
Sodium, Dietary
0
Aldosterone
4964P6T9RB
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NHLBI NIH HHS
ID : K24 HL103845
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL096518
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL104032
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL007609
Pays : United States
Informations de copyright
© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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