Estradiol (E2) inhibits fluid intake in several species, which may help to defend fluid homeostasis by preventing excessive extracellular fluid volume. Although this phenomenon is well established using the rat model, it has only been studied directly in young adults. Because aging influences the neuronal sensitivity to E2 and the fluid intake effects of E2 are mediated in the brain, we tested the hypothesis that aging influences the fluid intake effects of E2 in female rats. To do so, we examined water and NaCl intake in addition to the pressor effect after central angiotensin II treatment in young (3-4 months), middle-aged (10-12 months), and old (16-18 months) ovariectomized rats treated with estradiol benzoate (EB). As expected, EB treatment reduced water and NaCl intake in young rats. EB treatment, however, did not reduce water intake in old rats, nor did it reduce NaCl intake in middle-aged or old rats. The ability of EB to reduce blood pressure was, in contrast, observed in all three age groups. Next, we also measured the gene expression of estrogen receptors (ERs) and the angiotensin type 1 receptor (AT1R) in the areas of the brain that control fluid balance. ERβ, G protein estrogen receptor (GPER), and AT1R were reduced in the paraventricular nucleus of the hypothalamus in middle-aged and old rats, compared to young rats. These results suggest the estrogenic control of fluid intake is modified by age. Older animals lost the fluid intake effects of E2, which correlated with decreased ER and AT1R expression in the hypothalamus.

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Published in Physiological Reports, v. 9, issue 14.

© 2021 The Authors

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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This work was supported by the National Institutes of Health grant DA035150, NSF grant 2019346, and University of Kentucky, College of Arts and Sciences Start-Up Funds.

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The data that support the findings of this study are available from the corresponding author upon reasonable request.

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