mTORC1 Deficiency Modifies Volume Homeostatic Responses to Dietary Sodium in a Sex-Specific Manner
| Autor: | Stephen A. Maris, Jessica Lee, Shadi K Gholami, Gordon H. Williams, Thitinan Treesaranuwattana, Chee Sin Tay, Danielle L Brooks, Sanjay Ranjit, Gail K. Adler, Luminita H. Pojoga, Jose R. Romero, Amanda E Garza, Ezgi Caliskan Guzelce |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Time Factors Blood Pressure mTORC1 030204 cardiovascular system & hematology Mechanistic Target of Rapamycin Complex 1 Kidney 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Mineralocorticoid receptor Sex Factors Internal medicine Medicine Animals Homeostasis Salt intake Aldosterone PI3K/AKT/mTOR pathway business.industry Myocardium Sodium Dietary Regulatory-Associated Protein of mTOR 030104 developmental biology chemistry Renal blood flow Hypertension Female business Hormone Research Article Signal Transduction |
| Zdroj: | Endocrinology |
| DOI: | 10.5281/zenodo.3666819 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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