Acute Effects of Vitamin C on Platelet Responsiveness to Nitric Oxide Donors and Endothelial Function in Patients with Chronic Heart Failure

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Abstract
Chronic heart failure (CHF) is characterized by a prothrombotic state, which may relate to increased platelet aggregability, endothelial dysfunction, and increased oxidative stress. We investigated the effect of vitamin C in CHF on ex vivo platelet aggregation and platelet responsiveness to the anti-aggregatory effects of the nitric oxide (NO) donors glyceryl trinitrate (GTN) and sodium nitroprusside (SNP). We also examined parameters of oxidative stress and endothelial function in patients. In this double-blind, randomized, crossover study vitamin C (2 g) or placebo was given intravenously to 10 patients with CHF. We measured adenosine 5-diphosphate (ADP)-induced platelet aggregation, flow-mediated dilatation (FMD) in the brachial artery using ultrasonic wall-tracking, and plasma levels of lipid-derived free radicals using electron paramagnetic resonance spectroscopy. Vitamin C did not affect ex vivo platelet aggregability but enhanced the inhibition of platelet aggregation by SNP (62.7 ± 10.2 to 82.7 ± 4.8%, p = 0.03) and tended to increase responses to GTN (40.5 ± 9.0 to 53.4 ± 7.3, p = 0.06). The effect of vitamin C on platelet responsiveness to the anti-aggregatory effects of SNP was inversely related to basal response to SNP (r = −0.9, p r