Endothelial Function Response to Alterations in Sodium Vary with Energy Intake in Healthy, Normotensive Adults

High sodium intakes are a key contributor to cardiovascular disease burden. The Dietary Reference Intakes for sodium recommend all healthy individuals consume below 2,300 mg/d, regardless of energy needs. Newer evidence suggests the relation between sodium and blood pressure varies by energy intake. Whether the relation between sodium and endothelial dysfunction, a precursor to atherosclerosis, varies with energy intake in salt-resistant individuals is unknown. The objective of this secondary analysis was to determine if the magnitude of change in endothelial function on a low sodium diet vs a high sodium diet differs by energy level. We hypothesized that the magnitude of the change in endothelial function from low sodium to high sodium would be larger in individuals consuming fewer kcals. Twenty-three healthy young adults (15W/8M, age 28±6 y, BP 109±11/70±8 mmHg, BMI 24.9±2.8 kg/m 2 ) consumed a low sodium (1100 mg Na/d) and a high sodium (6900 mg Na/d) controlled diet for 10 days each in random order. Diets were customized to meet participants’ calculated energy needs. On day 10, endothelial function was assessed via brachial artery flow-mediated dilation (FMD), and mean difference in FMD from the low to high sodium diet (Δ%FMD) was calculated. Participants were evenly divided into three groups based on energy needs: low (1837±196 kcal/d), moderate (2262±58 kcal/d), and high (2543±215 kcal/d). For all participants, 24h ambulatory mean arterial pressure did not increase by ≥6 mmHg from the low to the high sodium diet, confirming salt resistance. Regardless of energy intake, %FMD was lower on the high sodium vs. low sodium diet (5.4±2.8% vs. 7.6±3.7%, p<0.001). Δ%FMD from the low sodium to high sodium diet was greatest in the low kcal group and smallest in the high kcal group (-2.80±2.6% vs. -2.38±3.2% vs. -1.44±1.9%) though group differences did not reach statistical significance (model p=0.61). The magnitude of change in dietary sodium density (mg Na/kcal, ΔNaDensity) from the low sodium to the high sodium diet was greatest in the low kcal group and smallest in the high kcal group (3.2±0.3 mg/kcal vs. 2.6±0.1 mg/kcal vs. 2.3±0.2, model p<0.001). After controlling for BMI, Δ%FMD was inversely correlated with ΔNaDensity (r=-0.44, p=0.02) such that a greater decline in %FMD is observed with a greater increase in dietary sodium density. Our findings suggest that FMD responses to alterations in sodium intake may vary with energy intake. This highlights the need to examine sodium relative to energy intake in future studies and when developing dietary intake recommendations for mitigating cardiovascular disease risk. AHA/VIVA 23POST1009835; NHLBI R01 HL145055 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.