Platelet activation, oxidative stress and overexpression of inducible nitric oxide synthase in moderate heart failure
| Autor: | Antonio C. Mendes-Ribeiro, Natália Rodrigues Pereira, Tatiana M.C. Brunini, Luisa Ribeiro de Meirelles, Cristiane Matsuura, Pedro G Cascarelli, Ângelo Antunes Salgado, Angela Castro Resende |
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| Rok vydání: | 2011 |
| Předmět: |
Pharmacology
medicine.medical_specialty biology Physiology Fibrinogen medicine.disease_cause Nitric oxide Superoxide dismutase Nitric oxide synthase chemistry.chemical_compound Endocrinology Biochemistry chemistry Physiology (medical) Internal medicine medicine biology.protein TBARS Platelet Platelet activation Oxidative stress medicine.drug |
| Zdroj: | Clinical and Experimental Pharmacology and Physiology. 38:705-710 |
| ISSN: | 0305-1870 |
| DOI: | 10.1111/j.1440-1681.2011.05580.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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