Impact of inorganic nitrate on renal sodium excretion during saline loading in healthy adults; secondary endpoints from a randomized crossover trial.

Inorganic nitrate may lower blood pressure (BP) and enhance natriuresis through nitric oxide (NO) mediated mechanisms. Studies have found inconsistent effects of NO on sodium excretion. Nitric oxide synthase (NOS) inhibition suggests increased NO promotes natriuresis, whereas inorganic nitrate studies remain inconclusive. We conducted a randomized, double-blind, placebo-controlled crossover trial in 18 healthy adults, with 4 days of potassium nitrate (KNO3) or placebo before 1 L isotonic saline infusion. BP, hemodynamic markers of the NO system, and renal function were measured. After saline GFR, renal water and sodium handling did not significantly differ between KNO3 and placebo (KCl). Central diastolic BP was modestly higher during KNO3 (p = 0.023). Brachial systolic BP did not differ (p = 0.052); however, systolic BP was higher during KNO3 after 120 min (Sidak adjusted, p = 0.030). Plasma levels of the second messenger of NO, cyclic guanosine monophosphate (cGMP), were lower after saline during KNO3 (p = 0.012). Short-term KNO3 did not induce a natriuretic response during acute saline loading. KNO3 was associated with a small increase in central diastolic BP and lower plasma cGMP levels. These findings suggest that high-dose KNO3 exposure may affect the endogenous NO response.