Abstract P113: Early Life Stress-Induced Increases in Urinary Aldosterone Precedes Renal Dysfunction and Hypertension in Male Mice Fed a High Fat Diet

Abstract

We have previously shown that mice subjected to maternal separation and early weaning (MSEW), a model of early life stress, display exacerbated angiotensin II-dependent obesity-induced hypertension and reduced glomerular filtration rate (GFR) after 16 weeks of high fat diet (HF). In this study, we hypothesized that renin-angiotensin aldosterone system (RAAS) activation in MSEW mice fed a HF for only 12 weeks will precede a decline in GFR and heightened hypertension. MSEW was performed by separating the pups from their mother for 4 to 8 hours from postnatal days (PD) 2 to 16. Mice were weaned at PD 17. Control mice remained undisturbed and were weaned at PD 21. We used 16 MSEW and 14 control litters. Eight-week-old mice were fed on a low fat diet (LF) or HF (10 or 60 % fat Kcal) for 12 weeks. Each litter was represented by one male randomly assigned to each diet. After 11 weeks, 24-hr urine was collected to measure proteins, creatinine, aldosterone and electrolytes by Duo ICAP-OES. At week 12, transcutaneous GFR and blood pressure were measured in all mice. Male MSEW and control mice fed a HF displayed similar blood pressure and metabolic parameters, including water intake (3.4±0.3 vs. 3.4±0.2 ml/day), diuresis (1.1±0.1 vs. 1.0±0.2 ml/day), natriuresis (0.10±0.01 vs. 0.09±0.01 mmol/day), proteinuria (3.5±0.7 vs. 2.9±0.5 mg/day) and GFR (0.97±0.04 vs. 0.96±0.03 ml/min/100g BW). However, MSEW increased kaliuresis (0.41±0.07 vs. 0.23±0.02 mmol/day, p<0.05) and urinary aldosterone (25±4 vs. 11±1 ng/g crea, p<0.05). In addition, MSEW mice displayed increased plasma aldosterone (158±32 vs. 87±17 pg/ml, p=0.056) and lower plasma renin concentration compared to controls (2.3±0.4 vs. 3.7±0.4 ng/mL/30’, p<0.05), suggesting elevated circulating angiotensin II. Only MSEW mice showed increased adiposity (36±1 vs. 24±4, %) and a positive correlation between urinary aldosterone and fat mass (2.6±0.9 vs. -0.1± 0.1, p<0.05). These data indicate that MSEW-induced RAAS overactivation precedes the increases in blood pressure and decline in GFR found in HF-fed mice later in life. Thus, increased angiotensin II, most likely due to elevated fat angiotensinogen, may stimulate adipocyte and/or adrenal-derived aldosterone production exacerbating obesity-hypertension in MSEW mice.