Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age.
BACKGROUND
The L-arginine/nitric oxide (NO) pathway has multiple physiological functions including vasodilation, inhibition of platelet aggregation and neurotransmission. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of all known NO synthase isoforms, has adverse effects on renal and cardiovascular function in adults. It is unknown whether ADMA might also exert similar effects in younger individuals including infants. Also, reference data for important members of the L-arginine/NO family, notably ADMA and the NO metabolites, nitrite and nitrate, in infancy are lacking.


METHODS
In the present study, we investigated the status of the L-arginine/NO pathway in 34 healthy volunteers aged 2 days to 24 years by measuring the concentration of ADMA, nitrite, nitrate and L-arginine in plasma and urine using gas chromatography-mass spectrometry and gas chromatography-tandem mass spectrometry methods.


RESULTS
We found that ADMA levels in plasma decreased with age (Pearson correlation coefficient r=-0.619, p<0.001). In contrast, urinary excretion of nitrate (r=0.471, p=0.036) and nitrite increased with age (r=0.484, p=0.037).


CONCLUSIONS
Our study suggests that in infants ADMA biosynthesis accompanied by an inhibition of NO synthesis is higher than in adults and diminishes considerably with age.
Lücke
Thomas
T
Department of Pediatrics, Hannover Medical School, Hannover, Germany. luecke.thomas@mh-hannover.de
Kanzelmeyer
Nele
N
Kemper
Markus J
MJ
Tsikas
Dimitrios
D
Das
Anibh M
AM
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*
C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine