Analysis of the L-Arginine / Nitric Oxide Pathway: The Unique Role of Mass Spectrometry

Abstract

Nitric oxide (NO) is a gaseous radical molecule. In human organism NO is produced in various cells from Larginine by the catalytical action of NO synthases (NOS). The L-arginine/NO pathway powerfully contributes to maintain multiple physiological functions, including vascular tone, platelet function and neurotransmission. The metabolic fate of NO is very complex due to the participation of numerous compounds resulting from the ability of NO to react practically with any biomolecule to produce biologically active metabolites (e.g. S-nitrosothiols) and biologically inactive metabolites (e.g. nitrate). The concentration in biological fluids and tissues of members of the L-arginine / NO family is of particular interest, as it may characterize the status of this pathway in health and disease as well as to monitor the progress of pharmacological interventions. Thus, measurement of the NO metabolites nitrate and nitrite is suitable to assess NO synthesis in vivo. On the other hand, measurement of the circulating NOS inhibitor asymmetric dimethylarginine (ADMA) was found to reliably identify pathological conditions associated with NO-related endothelial dysfunction. Among the various analytical methods currently available for the analysis of the L-arginine / NO family, mass spectrometry (MS)-based approaches such as gas chromatography-mass spectrometry (e.g. GC-MS / MS) and liquid chromatographymass spectrometry (e.g. LC-MS / MS) emerged indispensable analytical tools for the reliable quantitative analysis of the whole NO family. The present article discusses the currently available analytical methods especially emphasizing the importance of the MS technology to the NO field of research.