Acute effects of vitamin c on platelet responsiveness to nitric oxide donors and endothelial function in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by a prothrombotic state, whic h 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 (G TN) and sodium nitroprusside (SNP). We also examined parameters of oxidativ e stress and endothelial function in patients. In this double-blind, random ized, crossover study vitamin C (2 g) or placebo was given intravenously to 10 patients with CHF. We measured adenosine 5-diphosphate (ADP)-induced pl atelet aggregation, flow-mediated dilatation (FMD) in the brachial artery u sing ultrasonic wall-tracking, and plasma levels of lipid-derived free radi cals using electron paramagnetic resonance spectroscopy. Vitamin C did not affect ex vivo platelet aggregability but enhanced the inhibition of platel et 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 antiaggregatory effe cts of SNP was inversely related to basal response to SNP (r = -0.9, p < 0. 01); a similar trend was observed with GTN (r = -0.6, p = 0.1). Vitamin C a lso increased FMD (1.9 <plus/minus> 0.6 to 5.8 +/- 1.5%, p = 0.02) and redu ced plasma lipid-derived free radicals by 49 +/- 19% (p < 0.05). In patient s with CHF acute intravenous administration of vitamin C enhances platelet responsiveness to the anti-aggregatory effects of NO donors and improves en dothelial function, suggesting a potential role for vitamin C as a therapeu tic agent in CHF.