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Mechanistic target of 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 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 three volume homeostatic mechanisms---cardiovascular, renal and hormonal (aldosterone- sodium retaining and brain natriuretic peptide (BNP)- sodium losing)---were assessed in mTORC1 deficient (Raptor +/-) and wildtype male and female littermates at two different ages. The mice were volume stressed by giving 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, differ by sex.
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To compare the effects of two levels of dietary sodium on blood pressure in Black men and women, and to determine what factors predict the degree of response.
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Sodium or sodium compounds used in foods or as a food. The most frequently used compounds are sodium chloride or sodium glutamate.
Iron or iron compounds used in foods or as food. Dietary iron is important in oxygen transport and the synthesis of the iron-porphyrin proteins hemoglobin, myoglobin, cytochromes, and cytochrome oxidase. Insufficient amounts of dietary iron can lead to iron-deficiency anemia.
Dietary recommendations that promote reduction in or prevention of high blood pressure. Recommendations include increasing intake of fruits and vegetables, and high-fiber, low-fat foods and reducing the intake of DIETARY SODIUM and high fat foods.
Sodium chloride used in foods.
An AMILORIDE-sensitive sodium channel found on salt-reabsorbing EPITHELIAL CELLS that line the distal NEPHRON, the distal COLON; SALIVARY DUCTS; SWEAT GLANDS; and the LUNG. It plays a critical role in the control of sodium balance, BLOOD VOLUME, and BLOOD PRESSURE.
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