Nitrite and nitrate concentrations and metabolism in breast milk, infant formula, and parenteral nutrition.

Dietary nitrate and nitrite are sources of gastric NO, which modulates blood flow, mucus production, and microbial flora. However, the intake and importance of these anions in infants is largely unknown. Nitrate and nitrite levels were measured in breast milk of mothers of preterm and term infants, infant formulas, and parenteral nutrition. Nitrite metabolism in breast milk was measured after freeze-thawing, at different temperatures, varying oxygen tensions, and after inhibition of potential nitrite-metabolizing enzymes. Nitrite concentrations averaged 0.07 ± 0.01 µM in milk of mothers of preterm infants, less than that of term infants (0.13 ± 0.02 µM) (P < .01). Nitrate concentrations averaged 13.6 ± 3.7 µM and 12.7 ± 4.9 µM, respectively. Nitrite and nitrate concentrations in infant formulas varied from undetectable to many-fold more than breast milk. Concentrations in parenteral nutrition were equivalent to or lower than those of breast milk. Freeze-thawing decreased nitrite concentration ~64%, falling with a half-life of 32 minutes at 37°C. The disappearance of nitrite was oxygen-dependent and prevented by ferricyanide and 3 inhibitors of lactoperoxidase. Nitrite concentrations in breast milk decrease with storage and freeze-thawing, a decline likely mediated by lactoperoxidase. Compared to adults, infants ingest relatively little nitrite and nitrate, which may be of importance in the modulation of blood flow and the bacterial flora of the infant GI tract, especially given the protective effects of swallowed nitrite.

Nitrate reductase activity of bacteria in saliva of term and preterm infants.

The salivary glands of adults concentrate nitrate from plasma into saliva where it is converted to nitrite by bacterial nitrate reductases. Nitrite can play a beneficial role in adult gastrointestinal and cardiovascular physiology. When nitrite is swallowed, some of it is converted to nitric oxide (NO) in the stomach and may then exert protective effects in the gastrointestinal tract and throughout the body. It has yet to be determined either when newborn infants acquire oral nitrate reducing bacteria or what the effects of antimicrobial therapy or premature birth may be on the bacterial processing of nitrate to nitrite. We measured nitrate and nitrite levels in the saliva of adults and both preterm and term human infants in the early weeks of life. We also measured oral bacterial reductase activity in the saliva of both infants and adults, and characterized the species of nitrate reducing bacteria present. Oral bacterial conversion of nitrate to nitrite in infants was either undetectable or markedly lower than the conversion rates of adults. No measurable reductase activity was found in infants within the first two weeks of life, despite the presence of oral nitrate reducing bacteria such as Actinomyces odontolyticus, Veillonella atypica, and Rothia mucilaginosa. We conclude that relatively little nitrite reaches the infant gastrointestinal tract due to the lack of oral bacterial nitrate reductase activity. Given the importance of the nitrate-nitrite-NO axis in adults, the lack of oral nitrate-reducing bacteria in infants may be relevant to the vulnerability of newborns to hypoxic stress and gastrointestinal tract pathologies.

Inhaled nitric oxide therapy increases blood nitrite, nitrate, and s-nitrosohemoglobin concentrations in infants with pulmonary hypertension.

OBJECTIVE: To measure the circulating concentrations of nitric oxide (NO) adducts with NO bioactivity after inhaled NO (iNO) therapy in infants with pulmonary hypertension. STUDY DESIGN: In this single center study, 5 sequential blood samples were collected from infants with pulmonary hypertension before, during, and after therapy with iNO (n = 17). Samples were collected from a control group of hospitalized infants without pulmonary hypertension (n = 16) and from healthy adults for comparison (n = 12). RESULTS: After beginning iNO (20 ppm) whole blood nitrite levels increased approximately two-fold within 2 hours (P<.01). Whole blood nitrate levels increased to 4-fold higher than baseline during treatment with 20 ppm iNO (P<.01). S-nitrosohemoglobin increased measurably after beginning iNO (P<.01), whereas iron nitrosyl hemoglobin and total hemoglobin-bound NO-species compounds did not change. CONCLUSION: Treatment of pulmonary hypertensive infants with iNO results in increases in levels of nitrite, nitrate, and S-nitrosohemoglobin in circulating blood. We speculate that these compounds may be carriers of NO bioactivity throughout the body and account for peripheral effects of iNO in the brain, heart, and other organs.