Plasma and urine nitric oxide levels in healthy Turkish children

Abstract

Nitric oxide (NO) is an important messenger molecule with a wide range of actions in virtually all cell systems and organs. In kidneys it participates in glomerular and medullary hemodynamics, tubuloglomerular feed-back, renin secretion, and extracellular fluid balance. Although the role of NO in regulating renal function in adults is well-established, it has recently been suggested that NO has a more critical role in maintaining basal renal blood flow and glomerular filtration rate (GFR) in the developing kidney. NO is rapidly metabolized to the stable end products nitrite and nitrate, which are more slowly excreted into the urine. Thus these metabolites can be recommended as useful markers of endogenous NO synthase activity, despite limited data about age-related changes in in-vivo NO production. The aims of this study were to determine age-related normal reference values of serum and urinary NO metabolites and to assess the probable relationship between these metabolites and the GFR. Normal levels of NO end products in blood and urine of 296 healthy children (117 female, 179 male) between the ages of 0 and 16 were investigated, as was whether these values change with age. Serum and urinary nitrate levels did not differ according to sex. Serum nitrate levels are higher in younger children, especially in the newborn period, and decrease with age. Nitrate levels in urine are higher in younger children with a peak in infancy (1 month to 1 year) and decrease with age. It was demonstrated that this decrease in serum and urinary nitrate levels with age parallels the increase in GFR. In conclusion, urinary NO products may be an indirect marker of serum NO levels and NO might have an important regulatory function both in the maintenance of renal function and in the maturation of the developing kidneys.

A Noninvasive, Sensitive, Specific, and Reliable Approach to Assess Whole-Body Nitric Oxide Synthesis in Children

“…This finding agrees with other independent research groups who reported high levels of urinary nitrate excretion (index of NO synthesis) in infancy that declined with age (35)(36)(37). A similar age-related decrease was also observed in plasma (6,37) and cerebrospinal fluid nitrate concentrations (38). Furthermore, analyzing the data presented in a previous study of convalescent, treated newborns with pulmonary hypertension (5) 15 N]nitrate enrichments in the range of 0.5%-1.2% with mass spectrometry.…”

“…However, multiple regression analysis showed age as the only predictor variable of whole-body NO synthesis, suggesting that normal aging modulates NO homeostasis in children. This finding agrees with other independent research groups who reported high levels of urinary nitrate excretion (index of NO synthesis) in infancy that declined with age (35)(36)(37). A similar age-related decrease was also observed in plasma (6,37) and cerebrospinal fluid nitrate concentrations (38).…”

Urinary Nitrate Might Be an Early Biomarker for Pediatric Acute Kidney Injury in the Emergency Department

“…Recent findings have suggested that endothelial injury acts as a primary event leading to renal hypoxia with disturbances in NO pathways playing a major role (12). Studies have suggested that these metabolites may be useful markers of endogenous NO synthase activity (17). Thus, diminished urinary nitrate in patients with early AKI may reflect diminished endothelial production of NO and suggests targeting the NO pathway as a means to treat or prevent the development of AKI.…”

Evaluation of urinary biomarkers of oxidative/nitrosative stress in children with Down syndrome

“…However, a negative correlation of NOx with age was found in controls but not in DS. It has been reported that the tendency of urinary nitrate levels to decrease with age in healthy children may be a reflection of an age-related increase in GFR (Elli et al, 2005), so GFR could be impaired in DS.…”