Production and excretion of nitrate by human newborn infants: Neonates arenot little adults

Endothelium-derived relaxing factor, identified as nitric oxide or its addu cts, is metabolized to nitrate and excreted in the urine. Since blood press ures are lower in newborn infants compared to adults, we hypothesized that newborn infants would have increased excretion of nitrate on the day of bir th. Neonatal urine was collected before 24 h of age when exogenous intake o f nitrate was low. Two different analytical methods showed that nitrate acc ounted for >99% of nitrogen oxides in urine of healthy neonates and adults. The absolute micromolar concentration of nitrate in urine from infants was significantly below that of adults. When nitrate content was standardized for the reduced renal function in the newborn infant (creatinine content) a nd body mass (kilogram weight), the concentration of nitrate in neonatal ur ine was significantly higher than that; of adults. Nitrate concentrations i n the urine of prematurely born infants were twice that of nitrate measured in urine from term infants. These findings suggested that nitric oxide is produced in larger intravascular quantities: in newborn infants versus adul ts. Thus, we postulated that nitric oxide released from a nitrosothiol woul d be metabolized to nitrate more readily by neonatal erythrocytes compared to red blood cells obtained from adults. Neonatal erythrocytes, suspended a t concentrations of 8, 12, or 16 g per deciliter of hemoglobin, produced 1. 7- to 2.1-fold more nitrate than equivalent hemoglobin concentrations of ad ult erythrocytes that were each incubated with S-nitroso-N-acetylpenicillam ine (100 mu M) over a 2-h period. Taken together, the studies of urinary ni trate in newborn infants and the ability of neonatal erythrocytes to genera te nitrate are consistent with a robust production of nitric oxide immediat ely afterbirth. (C) 2000 Academic Press.