Effect of sodium balance on levels of nitrates in healthy subjects: Posthoc analysis of a randomized, double‐blinded, placebo‐controlled, crossover study

Nitric oxide (NO) regulates renal sodium handling, but the relationship between sodium intake, NO synthesis, and nitrate/nitrite levels is unclear in humans. In a randomized, placebo-controlled, double-blinded, crossover study, 27 healthy subjects followed a 4-day low-sodium diet with either sodium chloride tablets or placebo daily, separated by a 3-week washout. Blood pressure, pulse wave velocity, and glomerular filtration rate were assessed. Blood and 24-h urine samples were analyzed for nitrate, nitrite, cyclic guanosine monophosphate (cGMP), and electrolytes. Plasma nitrate levels were lower after high sodium intake (p = 0.019), while plasma nitrite and cGMP levels remained unchanged. Urinary excretion of nitrate and nitrite did not differ, but nitrate clearance and fractional excretion increased (both p = 0.010). Renal handling of nitrite was unchanged. No significant differences were observed in blood pressure, pulse wave velocity, or glomerular filtration rate. When stratified by sex, females showed higher plasma nitrate after low sodium and a decrease after high sodium. Females decreased urinary nitrate excretion, whereas males remained stable. In conclusion, high sodium intake decreased plasma nitrate without increased excretion, suggesting greater nitrate utilization, particularly in females. ClinicalTrials.gov Identifier: NCT06968182.