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High salt intake activates the hypothalamic-pituitary-adrenal axis, amplifies the stress response, and alters tissue glucocorticoid exposure in mice
The excretion of glucocorticoids (prominent physiological stress hormones) is linked to levels of urinary sodium. Consuming large quantities of sodium in the diet is commonplace, and is linked to negative cardiovascular outcomes. In this study by Costello et al. (2022), the authors investigated the impact of a high salt diet on the function of the hypothalamic-pituitary-adrenal axis and concurrent glucocorticoid levels in a population of male C57BL/6 mice. The mice were placed on a high salt diet and observed from the second week of the experiment up to the eighth. The authors noted that following 2 weeks of a high dietary salt intake, the mice demonstrated increased sensitivity of the hypothalamic-pituitary-adrenal axis, seen by increased glucocorticoid secretion in response to stress (restraining). In addition, increased dietary salt intake elevated the levels of messenger RNA (mRNA) encoding for corticotropin-releasing hormone (Crh) and proopiomelanocortin (Pomc) in the hypothalamus and anterior pituitary, indicating heightened levels of hypothalamic-pituitary-adrenal axis activity, on top of an increase in the expression of cerebral and hepatic 11β-hydroxysteroid dehydrogenase Type 1 enzyme mRNA, responsible for glucocorticoid regeneration. The increase in circulating glucocorticoids was also accompanied by a reduction in hepatic mRNA encoding for circulating Corticosteroid-Binding Globulin. In the mice hippocampus, Fkbp5 mRNA (a marker of exposure to elevated glucocorticoid levels) was increased. Furthermore, the increase in circulating glucocorticoid levels leads to water retention by the kidneys (increase in the vasopressin marker copeptin). This increase was also coupled with a rise in anterior pituitary Tonebp and Avpr1b, which may indicate a role for vasopressin and copeptin in elevating the sensitivity of the hypothalamic-pituitary-adrenal axis. The authors conclude that elevated levels of dietary salt enhance the responsiveness to basal and stress-related glucocorticoid secretion, modulating glucocorticoid homeostasis on central, peripheral, and cellular levels. [NPID: Cortisol, glucocorticoid excess, glucocorticoid receptor, salt, stress]
Year: 2022
