Amino Acids

, Volume 47, Issue 9, pp 1779–1793 | Cite as

A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from l-arginine or nitrite?

  • Stepan GambaryanEmail author
  • Dimitrios TsikasEmail author
Review Article
Part of the following topical collections:
  1. Homoarginine, Arginine and Relatives


The NO/sGC/cGMP/PKG system is one of the most powerful mechanisms responsible for platelet inhibition. In numerous publications, expression of functional NO synthase (NOS) in human and mouse platelets has been reported. Constitutive and inducible NOS isoforms convert l-arginine to NO and l-citrulline. The importance of this pathway in platelets and in endothelial cells for the regulation of platelet function is discussed since decades. However, there are serious doubts in the literature concerning both expression and functionality of NOS in platelets. In this review, we aim to present and critically evaluate recent data concerning NOS expression and function in platelets, and to especially emphasise potential pitfalls of detection of NOS proteins and measurement of NOS activity. Prevailing analytical problems are probably the main sources of contradictory data on occurrence, activity and function of NOS in platelets. In this review we also address issues of how these problems can be resolved. NO donors including organic nitrites (RONO) and organic nitrate (RONO2) are inhibitors of platelet activation. Endogenous inorganic nitrite (NO2 ), the product of NO autoxidation, and exogenous inorganic nitrite are increasingly investigated as NO donors in the circulation. The role of platelets in the generation of NO from nitrite is also discussed.


sGC cGMP Nitric oxide Mass spectrometry Nitric oxide synthase Pitfalls Platelets 



Carbonic anhydrase






Electron-capture negative-ion chemical ionization


Electron ionization


Gas chromatography


Soluble guanylyl cyclase


Cyclic guanosine monophosphate




(Lower) limit of detection


(Lower) limit of quantitation


Mass spectrometry




Nitric oxide


Nitric oxide synthase


Endothelial NOS


Inducible NOS


Neuronal NOS






Pentafluorobenzyl bromide


cGMP-dependent protein kinase


Relative standard deviation


Selected-ion monitoring


Vasodilator stimulated phosphoprotein


von Wildebrandt factor/ristocetin



Financial support was granted to SG (Russian Fund of Fundamental Research 15-04-02438) and to DT (TS 60/4-1) from the Deutsche Forschungsgemeinschaft (Germany). We thank the reviewers for their useful comments and suggestions which helped improve our manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The studies reported in this article were approved by the Ethics Committee of the Hannover Medical School.


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Copyright information

© Springer-Verlag Wien 2015

Authors and Affiliations

  1. 1.Sechenov Institute of Evolutionary Physiology and BiochemistryRussian Academy of SciencesSt. PetersburgRussia
  2. 2.Centre of Pharmacology and Toxicology, Bioanalytical Laboratory for Nitric Oxide, Oxidative Stress and Eicosanoids (BIOFORNOX20)Hannover Medical SchoolHannoverGermany

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