title: Nitric oxide activity in platelets of dengue haemorrhagic fever patients: the apparent paradoxical role of ADMA and l-NMMA.
abstract: Dengue haemorrhagic fever (DHF) is a prevalent acute disease that occurs in patients infected by an arbovirus in tropical and subtropical regions. We have previously shown increased intraplatelet nitric oxide (NO) production in patients with dengue fever associated with reduced platelet aggregation. In this study, l-arginine transport as well as expression and activity of nitric oxide synthase (NOS) isoforms in the presence or absence of l-arginine analogues were examined in 23 DHF patients. l-arginine transport and NOS activity in platelets were increased in patients with DHF compared with controls. However, platelet endothelial NOS (eNOS) and inducible (iNOS) protein levels did not differ between healthy controls and DHF patients. Endogenous or exogenous analogues did not inhibit platelet NOS activity from DHF patients. In contrast, endogenous l-arginine analogues [N(G)-monomethyl-l-arginine (l-NMMA) and asymmetric dimethylarginine (ADMA)] inhibited NOS activity in platelets from healthy subjects. These results show the first evidence that the intraplatelet l-arginine-NO pathway is activated in DHF patients. The lack of inhibition of NO formation in vitro by all l-arginine analogues tested in DHF platelets may suggest another mechanism by which NOS activity can be regulated.
authors.affiliation: Departamento de Farmacologia e Psicobiologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Av. 28 de Setembro 87, Rio de Janeiro 22551-030, Brazil.
authors.forename: Cristiane
authors.initials: C
authors.lastname: Matsuura
authors.forename: Thalyta L
authors.initials: TL
authors.lastname: Moraes
authors.forename: Julia B
authors.initials: JB
authors.lastname: Barbosa
authors.forename: Monique B
authors.initials: MB
authors.lastname: Moss
authors.forename: Mariana A S
authors.initials: MA
authors.lastname: Siqueira
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: Miguel Lemos
authors.initials: ML
authors.lastname: Neto
authors.forename: Tatiana M C
authors.initials: TM
authors.lastname: Brunini
authors.forename: Antonio Claudio
authors.initials: AC
authors.lastname: Mendes-Ribeiro
mesh_terms: D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects*; D001938:Brazil; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase; D010974:Platelet Aggregation; D019595:Severe Dengue / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D019323:omega-N-Methylarginine / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; C018524:N,N-dimethylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase