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Comprehensive analysis of the l-arginine/l-homoarginine/nitric oxide pathway in preterm neonates: potential roles for homoarginine and asymmetric dimethylarginine in foetal growth

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Abstract

l-Arginine (Arg) and l-homoarginine (hArg) are precursors of nitric oxide (NO), a signalling molecule with multiple important roles in human organism. In the circulation of adults, high concentrations of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) and low concentrations of hArg emerged as cardiovascular risk factors. Yet, the importance of the Arg/hArg/NO pathway, especially of hArg and ADMA, in preterm neonates is little understood. We comprehensively investigated the Arg/hArg/NO pathway in 106 healthy preterm infants (51 boys, 55 girls) aged between 23 + 6 and 36 + 1 gestational weeks. Babies were divided into two groups: group I consisted of 31 babies with a gestational age of 23 + 6 – 29 + 6 weeks; group II comprised 75 children with a gestational age of 30 + 0 – 36 + 1 weeks. Plasma and urine concentrations of ADMA, SDMA, hArg, Arg, dimethylamine (DMA) which is the major urinary ADMA metabolite, as well as of nitrite and nitrate, the major NO metabolites, were determined by GC–MS and GC–MS/MS methods. ADMA and hArg plasma levels, but not the hArg/ADMA molar ratio, were significantly higher in group II than in group I: 895 ± 166 nM vs. 774 ± 164 nM (P = 0.001) for ADMA and 0.56 ± 0.04 µM vs. 0.48 ± 0.08 µM (P = 0.010) for hArg. There was no statistical difference between the groups with regard to urinary ADMA (12.2 ± 4.6 vs 12.8 ± 3.6 µmol/mmol creatinine; P = 0.61) and urinary SDMA. Urinary hArg, ADMA, SDMA correlated tightly with each other. Urinary excretion of DMA was slightly higher in group I compared to group II: 282 ± 44 vs. 247 ± 35 µmol/mmol creatinine (P = 0.004). The DMA/ADMA molar ratio in urine was tendentiously higher in neonates of group I compared to group II: 27 ± 13 vs. 20 ± 5 (P = 0.065). There were no differences between the groups with respect to Arg in plasma and to nitrite and nitrate in plasma and urine. In preterm neonates, ADMA and hArg biosynthesis increases with gestational age without remarkable changes in the hArg/ADMA ratio or NO biosynthesis. Our study suggests that ADMA and hArg are involved in foetal growth.

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Abbreviations

ADMA:

Asymmetric dimethylarginine

AGAT:

Arginine:glycine amidinotransferase

CA:

Carbonic anhydrase

DDAH:

Dimethylarginine dimethylaminohydrolase

DMA:

Dimethylamine

DMD:

Duchenne muscular dystrophy

GAMT:

Guanidinoacetate methyltransferase

GC-MS:

Gas chromatography–mass spectrometry

GC-MS/MS:

Gas chromatography–tandem mass spectrometry

GHD:

Growth hormone deficiency

hArg:

Homoarginine

NO:

Nitric oxide

NOS:

NO synthase

SDMA:

Symmetric dimethylarginine

T1DM:

Type 1 diabetes mellitus

UNOxR:

Urinary nitrate-to-nitrite molar ratio

References

  • Achan V, Broadhead M, Malaki M, Whitley G, Leiper J, MacAllister R et al (2003) Asymmetric dimethylarginine causes hypertension and cardiac dysfunction in humans and is actively metabolized by dimethylarginine dimethylaminohydrolase. Arterioscler Thromb Vasc Biol 23:1455–1459

    Article  CAS  PubMed  Google Scholar 

  • Al Banchaabouchi M, Marescau B, Possemiers I, D’Hooge R, Levillain O, De Deyn PP (2000) NG, NG-dimethylarginine and NG, NG-dimethylarginine in renal insufficiency. Pflugers Arch 439:524–531

    CAS  PubMed  Google Scholar 

  • Alesutan I, Feger M, Tuffaha R, Castor T, Musculus K, Buehling SS et al (2016) Augmentation of phosphate-induced osteo-/chondrogenic transformation of vascular smooth muscle cells by homoarginine. Cardiovasc Res 110:408–418

    Article  PubMed  Google Scholar 

  • Atzler D, Schwedhelm E, Nauck M, Ittermann T, Böger RH, Friedrich N (2014) Serum reference intervals of homoarginine, ADMA, and SDMA in the study of health in Pomerania. Clin Chem Lab Med 52:1835–1842

    Article  CAS  PubMed  Google Scholar 

  • Atzler D, Appelbaum S, Cordts K, Ojeda FM, Wild PS, Münzel T, Blankenberg S, Böger RH, Blettner M, Beutel ME, Pfeiffer N, Zeller T, Lackner KJ, Schwedhelm E (2016a) Reference intervals of plasma homoarginine from the German Gutenberg Health Study. Clin Chem Lab Med 54:1231–1237

    Article  CAS  PubMed  Google Scholar 

  • Atzler D, Schönhoff M, Cordts K, Ortland I, Hoppe J, Hummel FC, Gerloff C, Jaehde U, Jagodzinski A, Böger RH, Choe CU, Schwedhelm E (2016b) Oral supplementation with l-homoarginine in young volunteers. Br J Clin Pharmacol. doi:10.1111/bcp.13068

    PubMed  Google Scholar 

  • Bassareo PP, Puddu M, Flore G, Deidda M, Manconi E, Melis A, Fanos V, Mercuro G (2012) Could ADMA levels in young adults born preterm predict an early endothelial dysfunction? Int J Cardiol 159:217–219

    Article  CAS  PubMed  Google Scholar 

  • Böger RH, Bode-Böger SM, Thiele W, Junker W, Alexander K, Frolich JC (1997a) Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease. Circulation 95:2068–2074

    Article  PubMed  Google Scholar 

  • Böger RH, Bode-Böger SM, Brandes RP, Phivthong-ngam L, Bohme M, Nafe R et al (1997b) Dietary l-arginine reduces the progression of atherosclerosis in cholesterol-fed rabbits: comparison with lovastatin. Circulation 96:1282–1290

    Article  PubMed  Google Scholar 

  • Böger RH, Bode-Böger SM, Szuba A, Tsao PS, Chan JR, Tangphao O et al (1998) Asymmetric dimethylarginine (ADMA): a novel risk factor for endothelial dysfunction: its role in hypercholesterolemia. Circulation 98:1842–1847

    Article  PubMed  Google Scholar 

  • Carmann C, Lilienthal E, Weigt-Usinger K, Schmidt-Choudhury A, Hörster I, Kayacelebi AA, Beckmann B, Chobanyan-Jürgens K, Tsikas D, Lücke T (2015) The l-arginine/NO pathway, homoarginine, and nitrite-dependent renal carbonic anhydrase activity in young people with type 1 diabetes mellitus. Amino Acids 47:1865–1874

    Article  CAS  PubMed  Google Scholar 

  • Chobanyan-Jürgens K, Schwarz A, Böhmer A, Beckmann B, Gutzki FM, Michaelsen JT, Stichtenoth DO, Tsikas D (2012) Renal carbonic anhydrases are involved in the reabsorption of endogenous nitrite. Nitric Oxide 26:126–131

    Article  PubMed  Google Scholar 

  • Cooke JP, Dzau VJ (1997) Nitric oxide synthase: role in the genesis of vascular disease. Annu Rev Med 48:489–509

    Article  CAS  PubMed  Google Scholar 

  • Ellery SJ, LaRosa DA, Kett MM, Della Gatta PA, Snow RJ, Walker DW, Dickinson H (2016) Dietary creatine supplementation during pregnancy: a study on the effects of creatine supplementation on creatine homeostasis and renal excretory function in spiny mice. Amino 48:1819–1830

    Article  CAS  Google Scholar 

  • Elli M, Soylemezoglu O, Erbas D, Bakkaloglu SA, Buyan N, Ozkaya O et al (2005) Plasma and urine nitric oxide levels in healthy Turkish children. Pediatr Nephrol 20:1605–1609

    Article  PubMed  Google Scholar 

  • Förstermann U (2006) Endothelial NO synthase as a source of NO and superoxide. Eur J Clin Pharmacol 62(Suppl 13):5–12

    Article  Google Scholar 

  • Frenay AR, Kayacelebi AA, Beckmann B, Soedamah-Muhtu SS, de Borst MH, van den Berg E, van Goor H, Bakker SJ, Tsikas D (2015a) High urinary homoarginine excretion is associated with low rates of all cause mortality and graft failure in renal transplant recipients. Amino Acids 47(9):1827–1836

  • Frenay AR, van den Berg E, de Borst MH, Beckmann B, Tsikas D, Feelisch M, Navis G, Bakker SJ, van Goor H (2015b) Plasma ADMA associates with all-cause mortality in renal transplant recipients. Amino Acids 47(9):1941–1949

  • Goonasekera CD, Rees DD, Woolard P, Frend A, Shah V, Dillon MJ (1997) Nitric oxide synthase inhibitors and hypertension in children and adolescents. J Hypertens 15:901–909

    Article  CAS  PubMed  Google Scholar 

  • Gorenflo M, Zheng C, Werle E, Fiehn W, Ulmer HE (2001) Plasma levels of asymmetrical dimethyl-l-arginine in patients with congenital heart disease and pulmonary hypertension. J Cardiovasc Pharmacol 37:489–492

    Article  CAS  PubMed  Google Scholar 

  • Hanff E, Kayacelebi AA, Herrmann C, Obermann M, Das AM, Tsikas D (2016) Unaltered l-arginine/NO pathway in a MELAS patient: Is mitochondrial NO synthase involved in the MELAS syndrome? Int J Cardiol 223:479–481

    Article  PubMed  Google Scholar 

  • Haynes WG, Noon JP, Walker BR, Webb DJ (1993) Inhibition of nitric oxide synthesis increases blood pressure in healthy humans. J Hypertens 11:1375–1380

    Article  CAS  PubMed  Google Scholar 

  • Hörster I, Weigt-Usinger K, Carmann C, Chobanyan-Jürgens K, Köhler C, Schara U, Kayacelebi AA, Beckmann B, Tsikas D, Lücke T (2015) The l-arginine/NO pathway and homoarginine are altered in Duchenne muscular dystrophy and improved by glucocorticoids. Amino Acids 47:1853–1863

    Article  PubMed  Google Scholar 

  • Jaźwińska-Kozuba A, Martens-Lobenhoffer J, Kruszelnicka O, Rycaj J, Chyrchel B, Surdacki A, Bode-Böger SM (2013) Opposite associations of plasma homoarginine, and ornithine with arginine in healthy children and adolescents. Int J Mol Sci 14:21819–21832

    Article  PubMed  Google Scholar 

  • Kayacelebi AA, Beckmann B, Gutzki FM, Jordan J, Tsikas D (2014) GC-MS and GC-MS/MS measurement of the cardiovascular risk factor homoarginine in biological samples. Amino Acids 46:2205–2217

    Article  CAS  PubMed  Google Scholar 

  • Kayacelebi AA, Knöfel AK, Beckmann B, Hanff E, Warnecke G, Tsikas D (2015a) Measurement of unlabeled and stable isotope-labeled homoarginine, arginine and their metabolites in biological samples by GC-MS and GC-MS/MS. Amino Acids 47:2023–2034

    Article  CAS  PubMed  Google Scholar 

  • Kayacelebi AA, Langen J, Weigt-Usinger K, Chobanyan-Jürgens K, Mariotti F, Schneider JY, Rothmann S, Frölich JC, Atzler D, Choe CU, Schwedhelm E, Huneau JF, Lücke T, Tsikas D (2015b) Biosynthesis of homoarginine (hArg) and asymmetric dimethylarginine (ADMA) from acutely and chronically administered free l-arginine in humans. Amino Acids 47:1893–1908

    Article  CAS  PubMed  Google Scholar 

  • Khalil A, Hardman L, O Brien P (2015) The role of arginine, homoarginine and nitric oxide in pregnancy. Amino Acids 47(9):1715–1727

  • Khalil AA, Tsikas D, Akolekar R, Jordan J, Nicolaides KH (2013) Asymmetric dimethylarginine, arginine and homoarginine at 11-13 weeks’ gestation and preeclampsia: a case-control study. J Hum Hypertens 27:38–43

    Article  CAS  PubMed  Google Scholar 

  • Kielstein JT, Böger RH, Bode-Böger SM, Schaffer J, Barbey M, Koch KM et al (1999) Asymmetric dimethylarginine plasma concentrations differ in patients with end-stage renal disease: relationship to treatment method and atherosclerotic disease. J Am Soc Nephrol 10:594–600

    CAS  PubMed  Google Scholar 

  • Kielstein JT, Impraim B, Simmel S, Bode-Böger SM, Tsikas D, Frölich JC, Hoeper MM, Haller H, Fliser D (2004) Cardiovascular effects of systemic nitric oxide synthase inhibition with asymmetrical dimethylarginine in humans. Circulation 109:172–177

    Article  CAS  PubMed  Google Scholar 

  • Kielstein JT, Tsikas D, Fliser D (2006) Effects of asymmetric dimethylarginine (ADMA) infusion in humans. Eur J Clin Pharmacol 62(Suppl 13):39–44

    Article  CAS  Google Scholar 

  • Kielstein A, Tsikas D, Galloway GP, Mendelson JE (2007) Asymmetric dimethylarginine (ADMA): a modulator of nociception in opiate tolerance and addiction? Nitric Oxide 17:55–59

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimoto M, Whitley GS, Tsuji H, Ogawa T (1995) Detection of NG, NG-dimethylarginine dimethylaminohydrolase in human tissues using a monoclonal antibody. J Biochem (Tokyo) 117:237–238

    Article  CAS  Google Scholar 

  • Kleinbongard P, Dejam A, Lauer T, Jax T, Kerber S, Gharini P et al (2006) Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans. Free Radic Biol Med 40:295–302

    Article  CAS  PubMed  Google Scholar 

  • Langen J, Kayacelebi AA, Beckmann B, Weigt-Usinger K, Carmann C, Hörster I, Lilienthal E, Richter-Unruh A, Tsikas D, Lücke T (2015) Homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in short stature children without and with growth hormone deficiency: hArg and ADMA are involved differently in growth in the childhood. Amino Acids 47:1875–1883

    Article  CAS  PubMed  Google Scholar 

  • Leiper JM, Vallance P (2006) The synthesis and metabolism of asymmetric dimethylarginine (ADMA). Eur J Clin Pharmacol 62(Suppl 13):33–38

    Article  Google Scholar 

  • Li X, Bazer FW, Johnson GA, Burghardt RC, Frank JW, Dai Z, Wang J, Wu Z, Shinzato I, Wu G (2014) Dietary supplementation with l-arginine between days 14 and 25 of gestation enhances embryonic development and survival in gilts. Amino Acids 46:375–384

    Article  CAS  PubMed  Google Scholar 

  • Lücke T, Tsikas D, Kanzelmeyer NK, Vaske B, Das AM (2006a) Elevated plasma concentrations of endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine in citrullinemia. Metabolism 55:1599–1603

    Article  PubMed  Google Scholar 

  • Lücke T, Tsikas D, Kanzelmeyer NK, Boerkoel CF, Clewing JM, Vaske B et al (2006b) Vaso-occlusion in Schimke-immuno-osseous dysplasia: is the NO pathway involved? Horm Metab Res 38:678–682

    Article  PubMed  Google Scholar 

  • Lücke T, Kanzelmeyer N, Kemper MJ, Tsikas D, Das AM (2007) Developmental changes in the l-arginine/nitric oxide pathway from infancy to adulthood: plasma asymmetric dimethylarginine levels decrease with age. Clin Chem Lab Med 45:1525–1530

    Article  PubMed  Google Scholar 

  • Lundman P, Eriksson MJ, Stuhlinger M, Cooke JP, Hamsten A, Tornvall P (2001) Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine. J Am Coll Cardiol 38:111–116

    Article  CAS  PubMed  Google Scholar 

  • Maas R, Böger RH (2003) Old and new cardiovascular risk factors: from unresolved issues to new opportunities. Atheroscler Suppl 4:5–17

    Article  PubMed  Google Scholar 

  • MacAllister RJ, Rambausek MH, Vallance P, Williams D, Hoffmann KH, Ritz E (1996) Concentration of dimethyl-l-arginine in the plasma of patients with end-stage renal failure. Nephrol Dial Transplant 11:2449–2452

    Article  CAS  PubMed  Google Scholar 

  • Marletta MA (1993) Nitric oxide synthase structure and mechanism. J Biol Chem 268:12231–12234

    CAS  PubMed  Google Scholar 

  • Moncada S, Bolanos JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97:1676–1689

    Article  CAS  PubMed  Google Scholar 

  • Moncada S, Higgs EA (2006) The discovery of nitric oxide and its role in vascular biology. Br J Pharmacol 147(Suppl 1):S193–S201

    CAS  PubMed  PubMed Central  Google Scholar 

  • Moonen RM, Huizing MJ, Cavallaro G, González-Luis GE, Bas-Suárez P, Bakker JA, Villamor E (2014) Plasma levels of dimethylarginines in preterm very low birth weight neonates: its relation with perinatal factors and short-term outcome. Int J Mol Sci 16:19–39

    Article  PubMed  PubMed Central  Google Scholar 

  • Papageorgiou N, Androulakis E, Papaioannou S, Antoniades C, Tousoulis D (2015) Homoarginine in the shadow of asymmetric dimethylarginine: from nitric oxide to cardiovascular disease. Amino Acids 47:1741–1750

    Article  CAS  PubMed  Google Scholar 

  • Pilz S, Meinitzer A, Gaksch M, Grübler M, Verheyen N, Drechsler C, Hartaigh BÓ, Lang F, Alesutan I, Voelkl J, März W, Tomaschitz A (2015) Homoarginine in the renal and cardiovascular systems. Amino Acids 47:1703–1713

    Article  CAS  PubMed  Google Scholar 

  • Rees D, Palmer R, Moncada S (1989) Role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sasso S, Dalmedico L, Magro DD, Pereira EM, Wyse AT, de Lima DD (2015) Differential in vitro effects of homoarginine on oxidative stress in plasma, erythrocytes, kidney and liver of rats in the absence and in the presence alpha-tocopherol, ascorbic acid or l-NAME. Amino Acids 47:1931–1939

    Article  CAS  PubMed  Google Scholar 

  • Savvidou MD, Hingorani AD, Tsikas D, Frölich JC, Vallance P, Nicolaides KH (2003) Endothelial dysfunction and raised plasma concentrations of asymmetric dimethylarginine in pregnant women who subsequently develop pre-eclampsia. Lancet 361:1511–1517

    Article  CAS  PubMed  Google Scholar 

  • Schlesinger S, Sonntag SR, Lieb W, Maas R (2016) Asymmetric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. PLoS One 11(11):e0165811

    Article  PubMed  PubMed Central  Google Scholar 

  • Surdacki A, Tsikas D, Mayatepek E, Frölich JC (2003) Elevated urinary excretion of nitric oxide metabolites in young infants with Zellweger syndrome. Clin Chim Acta 334:111–115

    Article  CAS  PubMed  Google Scholar 

  • Tolins JP, Palmer RM, Moncada S, Raij L (1990) Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol 258(3 Pt 2):H655–H662

    CAS  PubMed  Google Scholar 

  • Tsikas D (2000) Simultaneous derivatization and quantification of the nitric oxide metabolites nitrite and nitrate in biological fluids by gas chromatography/mass spectrometry. Anal Chem 72:4064–4072

    Article  CAS  PubMed  Google Scholar 

  • Tsikas D (2015) Circulating and excretory nitrite and nitrate: their value as measures of nitric oxide synthesis, bioavailability and activity is inherently limited. Nitric Oxide 45:1–3

    Article  CAS  PubMed  Google Scholar 

  • Tsikas D, Kayacelebi AA (2014) Do homoarginine and asymmetric dimethylarginine act antagonistically in the cardiovascular system? Circ J 78:2092–2093

    Article  Google Scholar 

  • Tsikas D, Wu G (2015) Homoarginine, arginine, and relatives: analysis, metabolism, transport, physiology, and pathology. Amino Acids 47:1697–1702

    Article  CAS  PubMed  Google Scholar 

  • Tsikas D, Böger RH, Sandmann J, Bode-Böger SM, Frölich JC (2000) Endogenous nitric oxide synthase inhibitors are responsible for the l-arginine paradox. FEBS Lett 478:1–3

    Article  CAS  PubMed  Google Scholar 

  • Tsikas D, Schubert B, Gutzki FM, Sandmann J, Frölich JC (2003) Quantitative determination of circulating and urinary asymmetric dimethylarginine (ADMA) in humans by gas chromatography-tandem mass spectrometry as methyl ester tri(N-pentafluoropropionyl) derivative. J Chromatogr B 798:87–99

    Article  CAS  Google Scholar 

  • Tsikas D, Gutzki FM, Stichtenoth DO (2006) Circulating and excretory nitrite and nitrate as indicators of nitric oxide synthesis in humans: methods of analysis. Eur J Clin Pharmacol 62(Suppl 13):51–59

    Article  CAS  Google Scholar 

  • Tsikas D, Thum T, Becker T, Pham VV, Chobanyan K, Mitschke A, Beckmann B, Gutzki FM, Bauersachs J, Stichtenoth DO (2007) Accurate quantification of dimethylamine (DMA) in human urine by gas chromatography-mass spectrometry as pentafluorobenzamide derivative: evaluation of the relationship between DMA and its precursor asymmetric dimethylarginine (ADMA) in health and disease. J Chromatogr B 851:229–239

    Article  CAS  Google Scholar 

  • Tsikas D, Wolf A, Mitschke A, Gutzki FM, Will W, Bader M (2010) GC-MS determination of creatinine in human biological fluids as pentafluorobenzyl derivative in clinical studies and biomonitoring: inter-laboratory comparison in urine with Jaffé, HPLC and enzymatic assays. J Chromatogr B 878:2582–2592

    Article  CAS  Google Scholar 

  • Vallance P, Leone A, Calver A, Collier J, Moncada S (1992a) Endogenous dimethylarginine as an inhibitor of nitric oxide synthesis. J Cardiovasc Pharmacol 20(Suppl 12):S60–S62

    Article  CAS  PubMed  Google Scholar 

  • Vallance P, Leone A, Calver A, Collier J, Moncada S (1992b) Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. Lancet 339:572–575

    Article  CAS  PubMed  Google Scholar 

  • Valtonen P, Laitinen T, Lyyra-Laitinen T, Raitakari OT, Juonala M, Viikari JS, Heiskanen N, Vanninen E, Punnonen K, Heinonen S (2008) Serum l-homoarginine concentration is elevated during normal pregnancy and is related to flow-mediated vasodilatation. Circ J 72:1879–1884

    Article  CAS  PubMed  Google Scholar 

  • Vida G, Sulyok E, Lakatos O, Ertl T, Martens-Lobenhoffer J, Bode-Böger SM (2009) Plasma levels of asymmetric dimethylarginine in premature neonates: its possible involvement in developmental programming of chronic diseases. Acta Paediatr 98:437–441

    Article  CAS  PubMed  Google Scholar 

  • Vida G, Sulyok E, Ertl T, Martens-Lobenhoffer J, Bode-Böger SM (2012) Birth by cesarean section is associated with elevated neonatal plasma levels of dimethylarginines. Pediatr Int 54:476–479

    Article  CAS  PubMed  Google Scholar 

  • Wu G (2013) Functional amino acids in nutrition and health. Amino Acids 45:407–411

    Article  CAS  PubMed  Google Scholar 

  • Wu G, Bazer FW, Davis TA, Kim SW, Li P, Marc Rhoads J, Carey Satterfield M, Smith SB, Spencer TE, Yin Y (2009) Arginine metabolism and nutrition in growth, health and disease. Amino Acids 37:153–168

    Article  CAS  PubMed  Google Scholar 

  • Wyse AT, Bavaresco CS, Hagen ME, Delwing D, Wannmacher CM, Severo Dutra-Filho C et al (2001) In vitro stimulation of oxidative stress in cerebral cortex of rats by the guanidino compounds accumulating in hyperargininemia. Brain Res 923:50–57

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Frank-Mathias Gutzki for performing the GC–MS and GC–MS/MS analyses.

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    Authors and Affiliations

    1. Department of Pediatrics, Hannover Medical School, Hannover, Germany

      Anna Buck & Kristine Chobanyan-Jürgens

    2. Centre of Pharmacology and Toxicology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany

      Arslan Arinc Kayacelebi, Bibiana Beckmann, Erik Hanff & Dimitrios Tsikas

    3. Institute of Clinical Pharmacology, Hannover Medical School, Hannover, Germany

      Kristine Chobanyan-Jürgens

    4. Clinic for Pediatric Kidney-, Liver- and Metabolic Diseases, Hannover Medical School Hannover, Hannover, Germany

      Sabine Illsinger & Anibh M. Das

    5. Department of Paediatric Pulmonology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany

      Bettina Bohnhorst

    6. Department of Neuropaediatrics, University Children’s Hospital, Ruhr University, Bochum, Germany

      Thomas Lücke

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    1. Anna Buck
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    The study was approved by the Ethics Committee of the Hannover Medical School.

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    A. Buck and A. A. Kayacelebi contributed equally to this work and are both first authors.

    D. Tsikas and T. Lücke contributed equally to this work and are both senior authors

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    Buck, A., Kayacelebi, A.A., Chobanyan-Jürgens, K. et al. Comprehensive analysis of the l-arginine/l-homoarginine/nitric oxide pathway in preterm neonates: potential roles for homoarginine and asymmetric dimethylarginine in foetal growth. Amino Acids 49, 783–794 (2017). https://doi.org/10.1007/s00726-017-2382-9

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