Persistent Changes in Salt Intake by Estrogen‐Treated Rats after Repeated Episodes of Dietary Sodium Deficiency

Abstract

AimsPrevious research from our lab and others demonstrated sex differences in sodium intake, though estrogen’s role in these differences is unclear. Further, previous studies analyzing salt intake with repeated episodes of sodium depletion using furosemide showed that stimulated salt intake was similar between males and females; however, there were clear sex differences in sodium intake after rats were no longer sodium depleted. We aimed to further elucidate the long‐term effects of estrogen on sodium intake using repeated episodes on a low salt diet, a more physiological challenge.MethodsOvariectomized rats were placed on two‐week periods of access to regular chow (NaR) or sodium deficient chow (NaD), which we alternated for a total of two exposures to each diet. Estrogen benzoate (EB) or oil injections were given twice weekly throughout the experiment. At the end of each diet period, rats were given a 2‐hour two bottle test (water and 0.5 M NaCl). At the end of the experiment, rats were sacrificed and trunk blood was collected and centrifuged to collect plasma. Plasma protein levels were measured. Uteri were collected and 1 cm segments of the uterine horns were weighed.ResultsWe confirmed the efficacy of EB treatment on body weight, uterine weight, and plasma proteins. As expected, EB‐treated rats maintained body weight throughout the experiment, with transient decreases, while oil‐treated rats gained weight. Both plasma proteins and uterine weights were greatly increased in EB‐treated compared to oil rats. During two‐bottle tests, both EB‐ and oil‐treated rats had similar baseline intakes of 0.5 M NaCl and water. When salt intake was stimulated by dietary sodium deficiency, both EB‐ and oil‐treated rats drank similarly increased amounts of 0.5 M NaCl. Interestingly, EB‐treated rats drank more 0.5 M NaCl and water than oil‐treated rats after returning to regular chow. The period of dietary sodium deficiency again elicited similar intakes of 0.5 M NaCl and water by EB‐ and oil‐treated rats.ConclusionsOur study demonstrated that estrogen did not alter induced salt intake induced by the physiological challenge, dietary sodium deficiency. However, the low salt diet led to persistent changes in behavior, as demonstrated by the continued consumption of salt and water by EB‐treated rats even after lost dietary sodium was replenished.