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.
Trans R Soc Trop Med Hyg. 2012 Mar;106(3):174-9. doi: 10.1016/j.trstmh.2011.10.009. Epub 2012 Jan 28.
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.
登革出血热（DHF）是一种流行于热带和亚热带地区、由虫媒病毒感染引起的急性疾病。我们之前的研究表明，登革热患者的血小板内一氧化氮（NO）生成增加，同时血小板聚集减少。在这项研究中，我们检测了 23 例登革热患者体内 l-精氨酸转运以及一氧化氮合酶（NOS）同工型的表达和活性，同时检测了有无 l-精氨酸类似物的情况下的上述指标。与对照组相比，DHF 患者的血小板内 l-精氨酸转运和 NOS 活性增加。然而，健康对照组和 DHF 患者的血小板内皮 NOS（eNOS）和诱导型（iNOS）蛋白水平没有差异。内源性或外源性类似物不能抑制 DHF 患者的血小板 NOS 活性。相反，内源性 l-精氨酸类似物[N（G）-单甲基-l-精氨酸（l-NMMA）和不对称二甲基精氨酸（ADMA）]抑制了健康受试者血小板中的 NOS 活性。这些结果首次表明，DHF 患者的血小板内 l-精氨酸-NO 途径被激活。在 DHF 患者的血小板中，所有测试的 l-精氨酸类似物在体外均不能抑制 NO 的形成，这可能提示了 NOS 活性可调节的另一种机制。
