Platelet activation, oxidative stress and overexpression of inducible nitric oxide synthase in moderate heart failure

Abstract

1. Chronic heart failure (CHF) is a common disabling disorder associated with thromboembolic events, the genesis of which is not yet fully understood. Nitric oxide (NO), derived from the vascular endothelium and platelets, has an important role in the physiological regulation of blood flow. It is generated from the amino acid L-arginine via NO synthase (NOS). 2. The main objective of the present study was to investigate NO production and its relationship with platelet aggregation, oxidative stress, inflammation and related amino acids in patients with moderate CHF. The expression and activity of NOS isoforms were analysed by western blotting and conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline, respectively, in CHF patients (n = 12) and healthy controls (n = 15). Collagen- and ADP-induced platelet aggregation, oxidative stress (thiobarbituric acid-reactive substances (TBARS) formation and superoxide dismutase (SOD) activity) and plasma levels of amino acids and inflammatory markers (fibrinogen and C-reactive protein (CRP)) were also determined. 3. Both collagen- and ADP-induced platelet aggregation were increased in CHF patients compared with controls. Platelets from CHF patients did not show any changes in NOS activity in the presence of overexpression of inducible NOS. Systemic and intraplatelet TBARS production was elevated, whereas SOD activity was decreased in CHF patients. l-arginine plasma concentrations were lower in CHF patients than in controls. Systemic levels of CRP and fibrinogen were increased in CHF patients. 4. The results show that, in patients with moderate CHF, there is platelet activation and reduced intraplatelet NO bioavailability due to oxidative stress, which suggests a role for platelets in the prothrombotic state.

An investigation of the antiplatelet effects of succinobucol (AGI-1067)

“…This may be either a direct effect of oxidant stress on the platelet [13] or an indirect effect through destruction of labile endothelium-derived vasodilators such as nitric oxide [14]. However, the direct effects of reactive oxygen species (ROS) on platelets are inconsistent with previous studies reporting both pro-and anti-aggregatory effects when platelets are exposed to exogenous ROS [15].…”

Platelet aggregometry cannot identify uremic platelet dysfunction in heart failure patients prior to cardiac surgery

“…In their cohort, patients were not taking aspirin but the majority were receiving beta-blockers, diuretics and angiotensin-converting enzyme inhibitors. [10]…”

The Nitric Oxide Donor Pentaerythritol Tetranitrate Reduces Platelet Activation in Congestive Heart Failure

“…This is mainly due to lack of evidence and due to the potential adverse effects like bleeding complications [ 35 ]. Significantly increased platelet activation is evident not only in severe heart failure or relying on the presence of atrial fibrillation but is also observed in patients with moderate heart failure [ 36 ] in sinus rhythm [ 37 ]. PETN prescription in heart failure is currently restricted to patients who are not eligible for coronary intervention but who still suffer from angina pectoris symptoms.…”