Effect of nitroxyl on human platelets function

Journal:Thrombosis and Haemostasis
ISSN:0340-6245
DOI:http://dx.doi.org/10.1160/TH05-01-0062
Issue:2005: 94/3 (Sep) pp. 469-691
Pages:578-584

Effect of nitroxyl on human platelets function

Emilse Bermejo2 , Daniel A. Sáenz 1 , Fabiana Alberto 2 , Ruth E. Rosenstein1 , Sara E. Bari3 , María A. L
1 Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, 2 Hemostasia y Trombosis, IIHEMA, Academia Nacional de Medicina de Buenos Aires, 3 Departamento de Química Inorgánica, Analítica y Química Física/ INQUIMAE, Facultad

Summary

There is a growing body of evidence on the role of nitric oxide(NO) in human platelet physiology regulation. Recently, interesthas developed in the functional role of an alternative redox formof NO, namely nitroxyl (HNO/NO- ), because it is formed by anumber of diverse biochemical reactions.The aim of the presentstudy was to comparatively analyze the effect of HNO and NOon several functional parameters of human platelets. For thispurpose, sodium trioxodinitrate (Angeli's salt, AS) and sodiumnitroprusside (SNP) were used as HNO and NO releasers, respectively.Both AS and SNP significantly inhibited platelet aggregationand ATP release induced by different agonists and adrenaline.AS or SNP did not modify the expression of platelet glycoproteins (Ib, IIb-IIIa, Ia-IIa, IV), whereas they substantially decreasedthe levels of CD62P, CD63 and of PAC-1 (a platelet activatedglycoprotein IIb/IIIa epitope) after the stimulation withADP.AS and SNP significantly increased cGMP accumulation ina 1H-[1,2,4]oxadiazolo [4,3-a] quinoxalin-1-one (ODQ)-sensitivemanner. However, while L-cysteine reduced the effect of AS,it increased the effect of SNP on this parameter.Accordingly, adifferential effect of L-cysteine was observed on the antiaggregatoryeffect of both compounds. In summary, these results indicatethat HNO is an effective inhibitor of human platelet aggregation.

DOI

http://dx.doi.org/10.1160/TH05-01-0062

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