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Enhanced Nitric Oxide (NO) and Decreased ADMA Synthesis in Pediatric ADHD and Selective Potentiation of NO Synthesis by Methylphenidate

1
University Children’s Hospital, Ruhr University Bochum, 44791 Bochum, Germany
2
Children’s Hospital, St., Clemens-Hospital Geldern, 47608 Geldern, Germany
3
Institute of Toxicology, Core Unit Proteomics, Hannover Medical School, 30625 Hannover, Germany
4
Department of Psychiatry, Alexius/Josef Hospital, 41464 Neuss, Germany
5
Department of Psychiatry, LWL Institute of Mental Health, LWL University Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
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Department of Psychiatry, LWL University Hospital, Ruhr-University Bochum, 44791 Bochum, Germany
7
LWL University Hospital Hamm for Child and Adolescent Psychiatry, Psychotherapy and Psychosomatic, Ruhr University Bochum, 59071 Hamm, Germany
*
Author to whom correspondence should be addressed.
Shared first author.
Shared senior author.
J. Clin. Med. 2020, 9(1), 175; https://doi.org/10.3390/jcm9010175 (registering DOI)
Received: 2 December 2019 / Revised: 27 December 2019 / Accepted: 4 January 2020 / Published: 8 January 2020
(This article belongs to the Special Issue Atherosclerosis: Endothelial Dysfunction and Beyond)
Attention deficit hyperactivity disorder (ADHD) is a common pediatric psychiatric disorder, frequently treated with methylphenidate (MPH). Recently, MPH’s cardiovascular safety has been questioned by observational studies describing an increased cardiovascular risk in adults and blood pressure alterations in children. We considered members of the L-arginine (Arg)/nitric oxide (NO) pathway as possible early cardiovascular risk factors in pediatric ADHD children. They include the NO metabolites, nitrite and nitrate, the NO precursor Arg, and asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor and a cardiovascular risk factor in adults. We conducted a prospective clinical trial with 42 ADHD children (aged 6–16 years) with (n = 19) and without (n = 23) MPH treatment. Age-matched children without ADHD (n = 43) served as controls. All plasma and urine metabolites were determined by gas chromatography-mass spectrometry. We observed higher plasma nitrite and lower plasma ADMA concentrations in the ADHD children. MPH-treated ADHD children had higher plasma nitrite concentrations than MPH-untreated ADHD children. As NOS activity is basally inhibited by ADMA, MPH treatment seems to have decreased the inhibitory potency of ADMA. Percentiles of systolic blood pressure were higher in MPH-treated ADHD children. The underlying mechanisms and their implications in the MPH therapy of pediatric ADHD with MPH remain to be elucidated in larger cohorts. View Full-Text
Keywords: L-Arg/NO pathway; cardiovascular risk; psychiatric disorder; pharmacotherapy; blood pressure regulation L-Arg/NO pathway; cardiovascular risk; psychiatric disorder; pharmacotherapy; blood pressure regulation
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Jansen, K.; Hanusch, B.; Pross, S.; Hanff, E.; Drabert, K.; Bollenbach, A.; Dugave, I.; Carmann, C.; Siefen, R.G.; Emons, B.; Juckel, G.; Legenbauer, T.; Tsikas, D.; Lücke, T. Enhanced Nitric Oxide (NO) and Decreased ADMA Synthesis in Pediatric ADHD and Selective Potentiation of NO Synthesis by Methylphenidate. J. Clin. Med. 2020, 9, 175.

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