title: Determination of cerebrospinal fluid concentrations of arginine and dimethylarginines in patients with subarachnoid haemorrhage.
abstract: Elevated cerebrospinal fluid (CSF) concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase (NOS), are assumed to be related to delayed vasospasm after subarachnoid haemorrhage (SAH). However, data on CSF concentrations of L-arginine, ADMA and its structural isomer symmetric dimethylarginine (SDMA) are very sparse in humans. We here present a new hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS-MS) method for the precise determination of these substances in CSF. The method requires only minimal sample preparation and features isotope labeled internal standards. First data of patients with SAH showed that on the day of admission CSF concentration values of L-arginine and ADMA were not significantly different from controls, but increased markedly during the course of the hospital stay. The decrease of the L-arginine to ADMA ratio points to a progressive impairment of the NO production rate in the brain after SAH which is confirmed by a simultaneous decrease in nitrate and nitrite concentrations in CSF.
authors.affiliation: Institute of Clinical Pharmacology, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. jens.martens-lobenhoffer@medizin.uni-magdeburg.de
authors.forename: Jens
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: Endre
authors.initials: E
authors.lastname: Sulyok
authors.forename: Endre
authors.initials: E
authors.lastname: Czeiter
authors.forename: Andras
authors.initials: A
authors.lastname: Büki
authors.forename: Jana
authors.initials: J
authors.lastname: Kohl
authors.forename: Raimund
authors.initials: R
authors.lastname: Firsching
authors.forename: Uwe
authors.initials: U
authors.lastname: Tröger
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Bode-Böger
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid*; D001921:Brain / Q000378:metabolism; D002555:Cerebrospinal Fluid / Q000737:chemistry*; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009448:Neurochemistry / Q000379:methods; D009566:Nitrates / Q000134:cerebrospinal fluid; D009569:Nitric Oxide / Q000096:biosynthesis; D009573:Nitrites / Q000134:cerebrospinal fluid; D013345:Subarachnoid Hemorrhage / Q000134:cerebrospinal fluid* / Q000175:diagnosis; D015854:Up-Regulation / Q000502:physiology
chemical_list: D009566:Nitrates; D009573:Nitrites; C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine