title: Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?
abstract: Epidemiological evidence has shown that platelet activation markers are consistently elevated in obesity, contributing to its prothrombotic state. In order to improve the understanding of the regulation of platelet function in obesity, the aim of this study was to investigate the l-arginine-nitric oxide (NO) pathway in obese adults without other cardiovascular risk factor. Seventeen obese (body mass index [BMI] 35.9±1.0 kg/m(2) ) and eighteen age-matched normal weight subjects (BMI 22.0±0.6 kg/m(2) ) were included in this study. l-arginine influx was measured with incubation of l-[(3) H]-arginine. NO synthase (NOS) and arginase activities were determined by the citrulline assay and the conversion of l-[(14) C]-arginine to [(14) C]-urea, respectively. Cyclic guanosine monophosphate (cGMP) content was evaluated by enzyme-linked immunosorbent assay. In addition, the study analyzed: platelet aggregation; intraplatelet antioxidant enzymes, via superoxide dismutase (SOD) and catalase activities; and systemic levels of l-arginine, fibrinogen, and C-reactive protein (CRP). Obese patients presented a significant decrease of platelet l-arginine influx, NOS activity, and cGMP levels, along with platelet hyperaggregability. On the presence of NO donor, platelet aggregation was similar between the groups. The fibrinogen and CRP systemic levels were significantly higher and SOD activity was reduced in obesity. No significant differences were observed in plasma levels of l-arginine and intraplatelet arginase and catalase activities between groups. The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity.
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Natália Rodrigues Pereira
authors.initials: NR
authors.lastname: Leite
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Mariana
authors.initials: M
authors.lastname: Siqueira de Medeiros
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Wanda Vianna
authors.initials: WV
authors.lastname: Mury
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matsuura
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|Discipline of Pharmacology, Department of Physiological Sciences, Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Monique Bandeira Moss
authors.initials: MB
authors.lastname: Perszel
authors.affiliation: Department of Internal Medicine, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Gerson
authors.initials: G
authors.lastname: Noronha Filho
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Tatiana Mc
authors.initials: TM
authors.lastname: Brunini
authors.affiliation: Department of Pharmacology and Psychobiology, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|Discipline of Pharmacology, Department of Physiological Sciences, Federal University of the State of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Antônio Claúdio
authors.initials: AC
authors.lastname: Mendes-Ribeiro
mesh_terms: D000328:Adult; D001120:Arginine / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D003430:Cross-Sectional Studies; D006152:Cyclic GMP / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000097:blood; D009765:Obesity / Q000097:blood* / Q000175:diagnosis; D018384:Oxidative Stress / Q000502:physiology*; D010974:Platelet Aggregation / Q000502:physiology*
chemical_list: D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP
keywords: cardiovascular disease; nitric oxide; obesity; oxidative stress; platelets