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Lean Mice Show Sex‐Specific Effects of Early Life Stress on Water and Electrolyte Homeostasis and Renal Function
Author(s) -
Ghuneim Sundus,
Leachman Jacqueline,
Dalmasso Carolina,
Loria Analia
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.02975
Subject(s) - medicine , endocrinology , excretion , weaning , renal function , homeostasis , litter , urine , blood pressure , chemistry , biology , agronomy
Early life stress (ELS) is associated with increases in body mass index and systolic blood pressure in adult life, leading to obesity and obesity‐induced hypertension, major risk factors for cardiovascular disease (CVD). Previously, we have shown that Maternal Separation and Early Weaning (MSEW), a model that mimics the effects of ELS observed in humans, exacerbates hypertensive stimuli responses in male and female mice. The aim of this study was to investigate the status of the water and electrolyte homeostasis (WEH) at baseline in mice exposed to MSEW. Therefore, we determined water intake and excretion, plasma and urinary electrolytes, glomerular filtration rate (GFR) and sodium transporters expression along the nephron in lean mice. MSEW litter pups were separated from dams from postnatal day (PND) 2 to 16, followed by early weaning on PND 17. Litters that remained undisturbed and were weaned on PND 21 served as controls. At weaning, mice were placed on a low‐fat diet (LF, 10% Kcal from fat) for 12 weeks. Single mouse metabolic cages were used to measure water intake and urine excretion. GFR was measured using a transcutaneous technique. MSEW males fed a LF showed an increase in water intake compared to controls (4.14 ± 0.32 vs. 3.4 ± 0.36 mL/day respectively, P<0.05), urine excretion (1.01 ± 0.16 vs. 0.61 ± 0.07 mL/day, P<0.05), and potassium excretion (12.05 ± 2.48 vs. 7.29 ± 1.49 µmol/day/g BW, P<0.05). MSEW mice showed no differences in plasma sodium (165.16 ± 2.44 vs. 161.34 ± 2.67 mmol/L), plasma potassium (5.42 ± 0.19 vs. 5.86 ± 0.16 mmol/L) or sodium excretion compared to controls (3.65 ± 0.72 vs. 3.24 ± 1.43 µmol/day/g BW, respectively). In addition, MSEW males showed increased GFR compared to controls (1.12 ± 0.05 vs. 0.90 ± 0.03 mL/min/100g BW, P<0.05). Renal cortex NHE3 expression was increased in MSEW compared to control mice (7.74 ± 2.22 vs. 1.2 ± 0.25 2^ddCt, respectively, P<0.05) while NCC expression was decreased compared to controls (0.38 ± 0.13 vs. 1.25 ± 0.32 2^ddCt respectively, P<0.05). Yet, no significant changes between MSEW and control mice were found in renal transporters NKCC2 (0.91 ± 0.26 vs. 1.23 ± 0.29 2^ddCt, respectively), or in the ENaC subunits ENaCα (0.97 ± 0.09 vs. 1.12 ± 0.21 2^ddCt), ENaCβ (1.14 ± 0.13 vs. 1.14 ± 0.27 2^ddCt), and ENaCγ (0.88 ± 0.13 vs. 1.08 ± 0.17 2^ddCt). Lean female MSEW mice showed no significant differences in water intake, urine excretion, urinary potassium, GFR, or renal transporters expression. Both increased NHE3 and reduced NCC expression have been linked to a greater potassium waste. These results show that the MSEW effects on WEH in lean mice are sex‐specific, where only male mice display hyperfiltration and alterations in specific renal transporters expression. Chronic hyperfiltration may result in kidney damage and over time, chronic kidney disease. This could be aggravated in animals exposed to a secondary stressor such as a high‐fat or high‐salt diet. Ongoing studies of plasma and urine osmolarity may provide insights into the potential mechanisms by which MSEW male mice show hyperfiltration in lean healthy and normotensive mice.