Asymmetric dimethyl arginine and symmetric dimethyl arginine levels in infants with persistent pulmonary hypertension of the newborn.
OBJECTIVE
We investigated whether infants with persistent pulmonary hypertension had elevated levels of asymmetric dimethyl arginine, an endogenous inhibitor of nitric oxide synthase, and symmetric dimethyl arginine, a regioisomer.


METHODS
Prospective observational cohort study.


METHODS
A 10-bed neonatal intensive care unit in a tertiary referral center.


METHODS
Forty five infants >34 wks gestation and <2 wks old admitted to our intensive care unit.


METHODS
Samples of urine on days 1, 3, and 5 were analyzed by high-performance liquid chromatography to determine asymmetric dimethyl arginine and symmetric dimethyl arginine levels. The clinical progression and treatment of the infants were noted.


RESULTS
Twenty-nine infants had a clinical diagnosis of persistent pulmonary hypertension confirmed on echocardiography, and there were 16 control infants. Median asymmetric dimethyl arginine levels on day 1 were significantly higher in the persistent pulmonary hypertension group (n = 29), 14.8 (10.3-21.7) mmol.mmol creatinine(-1).L(-1), compared with controls (n = 16), 3.6 (1.4-5.2) mmol.mmol creatinine(-1).L(-1) (p < .001). Asymmetric dimethyl arginine levels decreased to control levels by day 5 (p = .33). Symmetric dimethyl arginine levels were significantly higher than controls on day 1, 31.0 (21.7-65.9) vs. 14.7 (4.1-20.2) mmol.mmol creatinine(-1).L(-1) (p = .001) and day 3, 34.7(20.3-42.5) mmol.mmol creatinine(-1).L(-1) (p = .0001) and by day 5 had decreased significantly (p = .007) back to 16.7 (12.3-23.8) mmol.mmol creatinine(-1).L(-1), which was not significantly different than the control group values.


CONCLUSIONS
These results support the hypothesis that asymmetric dimethyl arginine and symmetric dimethyl arginine levels are elevated in patients with persistent pulmonary hypertension. Thus, endogenous inhibition of nitric oxide synthase by asymmetric dimethyl arginine may be responsible for the development of persistent pulmonary hypertension, suggesting novel therapeutic options in persistent pulmonary hypertension.
Pierce
Christine M
CM
Pediatric Intensive Care Unit and Department of Biochemistry, Great Ormond Street Hospital for Children NHS Trust, London.
Krywawych
Steven
S
Petros
Andy J
AJ
D001120:Arginine / Q000031:analogs & derivatives* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000652:urine*; D007231:Infant, Newborn; D015278:Intensive Care Units, Pediatric; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors
C487735:dimethylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase