Developmental changes in the L-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age

Abstract

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 rs-0.619, p-0.001). In contrast, urinary excretion of nitrate (rs0.471, ps0.036) and nitrite increased with age (rs0.484, ps0.037). 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. Clin Chem Lab Med 2007;45:1525-30.

The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids

“…Interestingly, ADMA synthesis is higher in children compared to adults, yet without signs of cardiovascular diseases. In healthy humans, ADMA synthesis decreases steadily from infancy to adulthood (Lücke et al 2007). We were interested to know whether the L-Arg/NO pathway is altered in children with DMD.…”

“…DMD patients affected more severely are usually older than less affected DMD patients. This circumstance and the age-dependent decrease of circulating ADMA in healthy children (Lücke et al 2007) may explain in part the lack of a correlation between plasma ADMA concentration and stage of disease in the DMD patients.…”

“…Elevated ADMA levels were found for example in children with hypertension (Goonasekera et al 1997) and citrullinemia (Lücke et al 2006a). Moreover, the developmental changes in the L-Arg/NO pathway from infancy to adulthood have been investigated (Lücke et al 2007). Thus, ADMA levels in plasma were found to decrease with age, 1 3 so that ADMA concentrations in young healthy controls are much higher than in healthy adults, while adolescents almost reach the levels prevailing in adulthood (Lücke et al 2007).…”

The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus

“…High ADMA levels have been found in adults with type 1 diabetes mellitus (T1DM) compared to healthy controls (Altinova et al 2007;Marcovecchio et al 2011). In previous studies, we reported on developmental changes in the Arg/NO pathway from infancy to adulthood, showing a decrease in plasma ADMA levels with age (Lücke et al 2007), as well as in metabolic diseases (Lücke et al 2006(Lücke et al , 2008ChobanyanJürgens et al 2012a;Kanzelmeyer et al 2012) (Fig. 1).…”

Does the Inhibitory Action of Asymmetric Dimethylarginine (ADMA) on the Endothelial Nitric Oxide Synthase Activity Explain Its Importance in the Cardiovascular System? The ADMA Paradox

“…The cardiovascular risk assigned to ADMA in adults is likely to arise from other not yet recognized actions of ADMA. Children have much higher circulating ADMA concentrations than adults (29), but there is no evidence that children have a risk for cardiovascular disease. In humans, the activity of eNOS, nNOS, and iNOS is steadily inhibited by ADMA and other endogenous inhibitors, and L-arginine administration can reduce the extent of this baseline inhibition to almost the same degree, albeit by different mechanisms.…”