Abstract Body: Extremely premature birth is a risk factor for sodium (Na) depletion due to renal immaturity and urine Na losses. We have proposed that Na depletion in preterm infants mechanistically contributes to their increased risk for cardiovascular and metabolic disease observed in adulthood, potentially due to changes during hypothalamic development. In humans, the hypothalamus matures between 20-25 weeks of gestation; in mice, this developmental window occurs between postnatal day (PD) 21 and PD42. Previously, we demonstrated in mice that dietary Na restriction from PD21 to PD42 induced long-lasting increases in energy expenditure via exaggerated autonomic activity. Therefore, we hypothesized that restricting dietary Na from PD21 to PD42 would similarly induce programmed changes in cardiovascular control via changes in autonomic and neurohypophyseal functions. Male C57BL/6J mice were provided a customized low (0.04%, n=7) or supplemented (0.30%, n=8) Na version of the soy protein-free Teklad 2920x diet from PD21 to PD42, after which they were returned to the standard (0.15% Na) 2920x diet. Radiotelemetric blood pressure (BP) transducers were implanted at 7-8 weeks of age. At 10 weeks of age, no differences in BP or heart rate (HR) were noted between groups. All animals were switched to a high (1%) Na diet at 12 weeks of age. At 16 weeks of age, systolic BP was not altered in the 0.30% Na group but significantly increased in the 0.04% Na group compared to the week 10 baseline (24h avg: +6±2 mmHg, p<0.05). Ganglionic block with chlorisondamine or β-adrenergic block with propranolol reduced heart rate (HR) to a greater extent (each p<0.05) in the 0.04% group. Conversely, muscarinic block with atropine resulted in a smaller increase in HR in this group (p<0.05). Urine elimination rates of aldosterone (0.30%: 1.96±0.44 vs 0.04%: 2.92±0.064 ng/d) and copeptin (0.30%: 0.16±0.03 vs. 0.04%: 0.14±0.02 ng/d) were similar between groups. Finally, at 18 weeks of age, all mice received the angiotensin AT₁R antagonist losartan in drinking water. This caused a greater BP reduction in the 0.04% group at 20 weeks (24h avg: -12±2 vs -19±2 mmHg, p<0.05). Together, these data indicate that dietary Na restriction during hypothalamic development programs increased salt sensitivity of BP via a mechanism involving AT₁R and characterized by increased sympathetic yet decreased parasympathetic activity.