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J Infect Dis. 2014 Sep 15;210(6):913-22. doi: 10.1093/infdis/jiu156. Epub 2014 Mar 11.

Dimethylarginines: endogenous inhibitors of nitric oxide synthesis in children with falciparum malaria.

Author information

1
Duke University and V.A. Medical Centers, Durham, North Carolina.
2
Menzies School of Health Research and Charles Darwin University, Australia.
3
Hubert Karuiki Memorial University, Dar es Salaam, Tanzania.
4
University of Utah and V.A. Medical Centers, Salt Lake City.

Abstract

BACKGROUND:

Nitric oxide (NO) bioavailability is impaired in children and adults with severe falciparum malaria (SM). Asymmetric-dimethylarginine (ADMA) limits NO production by inhibiting NO synthase and is increased in adult SM. The role of ADMA in the pathogenesis of childhood SM is unknown.

METHODS:

We studied Tanzanian children ages 4-8 years with malaria. Plasma levels of arginine, arginase, cell-free hemoglobin, ADMA, symmetric-dimethylarginine (SDMA), histidine-rich protein-2, and angiopoietin-2 were measured.

RESULTS:

ADMA was low in children with SM relative to controls. Nevertheless, arginine and arginine:ADMA ratios were very low in SM. SDMA was high in children with SM. With treatment, arginine and the arginine:ADMA ratio normalized, but SDMA did not. Arginine:ADMA ratios, but not arginine, were significantly and inde-pendent-ly inversely associated with lactate and angiopoietin-2. Plasma arginase was not elevated in those with malaria, and plasma free hemoglobin was elevated only in patients with cerebral malaria.

CONCLUSIONS:

In contrast to adults, plasma ADMA is reduced in SM in children, but hypoargininemia is more severe. Arginine bioavailability (reflected by low arginine:ADMA ratios) is therefore comparably low in SM in children as in adults. Therapies to increase NO bioavailability in malaria may be useful as adjunctive treatment of severe malaria in children.

KEYWORDS:

angiopoeitin 2; arginase; arginine; asymmetric dimethylarginine; falciparum malaria; lactate; nitric oxide; symmetric dimethylarginine

PMID:
24620026
PMCID:
PMC4192051
DOI:
10.1093/infdis/jiu156
[Indexed for MEDLINE]
Free PMC Article

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