Maternal low sodium intake and early postnatal diuretics program metabolic and ventilatory dysfunction in mice.

Abstract

Perinatal disruption of sodium homeostasis, which is critical for organ and cell function, may impact growth, metabolism, and pulmonary function. Two murine models were studied. First, maternal mice were supplied with a standard (0.15%) or low sodium (0.04% Na) diet from embryonic day 18 until postnatal day 21 (E18-P21). Second, offspring of mothers on standard Na were administered daily furosemide (30 mg/kg ip) on P10-P13 or sham injection. All pups received 0.15% Na diet at weaning. In male offspring, weight and body composition were serially measured while total energy expenditure was determined at 8-9 weeks of age. Ventilatory function was assessed at 3-5 weeks and again at 6-8 weeks of age in males and females. Lung structure was assessed at 9-10 weeks. Maternal low Na diet programmed significantly decreased weight gain in offspring associated with increased total energy expenditure. No significant effects on lung structure or breathing were seen. Furosemide resulted in increased weight, fat and fat-free mass in males. Furosemide was also associated with significantly decreased minute ventilation and tidal volume in males without changes to lung structure. Perinatal Na homeostasis is crucial for long-term growth, metabolism, and pulmonary function. Maintenance of early life sodium homeostasis is essential for growth and organ development Using different mouse models, we demonstrated a crucial role of early Na balance in long term growth, body composition, and metabolic and respiratory functions. Optimized intervention to maintain sodium homeostasis may improve long-term outcomes of preterm infants.