Platelet nitric oxide signalling in heart failure: role of oxidative stress

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Abstract

Aims Heart failure is associated with deficient endothelial nitric oxide (NO) production as well as increased oxidative stress and accelerated NO degradation. The aim of this study was to evaluate platelet NO biosynthesis and superoxide anion (O-2(-)) production in patients with heart failure. Methods and results In platelets from patients with heart failure due to idiopathic dilated cardiomyopathy (n = 16) and healthy control subjects (n = 23), NO synthase (NOS) activity was evaluated by L-[H-3]-arginine to L-[H-3]-citrulline conversion, cGMP was determined by radioimmunoassay, vasodilator-stimulated phosphoprotein (VASP: total and serine-239-phosphorylated) was assessed by western blotting, and O-2(-) production and O-2(-) scavenging capacity were measured by pholasin-enhanced chemiluminescence. In platelets from patients with heart failure, basal NOS activity was higher than in those from controls; furthermore, whereas platelet NOS activity increased as expected in response to albuterol or collagen in controls, no increase occurred in platelets from heart failure subjects. Despite this, basal intra-platelet NO-attributable cGMP was lower in heart failure than in control subjects, as was serine-239 phosphorylation of VASP, suggesting a decrease in bioactive NO. Platelets from heart failure subjects exhibited higher basal and collagen-stimulated O-2(-) production and impaired O-2(-) scavenging capacity, resulting in higher oxidative stress, consistent with the observed decrease in bioactive NO. Conclusion In heart failure, despite activation of NOS, platelets produce less bioactive NO, probably as a result of NO scavenging due to increased O-2(-) production. This functional defect in the platelet L-arginine/NO/guanylyl cyclase pathway could contribute to the platelet activation observed in heart failure.
Original languageEnglish
Pages (from-to)625 - 631
Number of pages7
JournalCardiovascular Research
Volume91
Issue number4
DOIs
Publication statusPublished - 1 Sept 2011

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