A review and discussion of platelet nitric oxide and nitric oxide synthase: do blood platelets produce nitric oxide from l-arginine or nitrite?
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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.
KeywordssGC cGMP Nitric oxide Mass spectrometry Nitric oxide synthase Pitfalls Platelets
Electron-capture negative-ion chemical ionization
Soluble guanylyl cyclase
Cyclic guanosine monophosphate
(Lower) limit of detection
(Lower) limit of quantitation
Nitric oxide synthase
cGMP-dependent protein kinase
Relative standard deviation
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.
The studies reported in this article were approved by the Ethics Committee of the Hannover Medical School.
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