Departamento de Farmacologia e Psicobiologia, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Blood Cells Mol Dis. 2010 Dec 15;45(4):338-42. doi: 10.1016/j.bcmd.2010.10.003.
Nitric oxide (NO) is a short-lived gaseous messenger with multiple physiological functions including regulation of blood flow, platelet adhesion and aggregation inhibition. NO synthases (NOS) catalyze the conversion of cationic amino acid L-arginine in L-citrulline and NO. Despite an increasing prevalence of obesity and metabolic syndrome (MetS) in the last decades, the exact mechanisms involved in the pathogenesis and cardiovascular complications are not fully understood. We have examined the effects of obesity and MetS on the L-arginine-NO-cGMP pathway in platelets from a population of adolescents.
A total of twenty six adolescent patients (13 with obesity and 13 with MetS) and healthy volunteers (n=14) participated in this study. Transport of L-arginine, NO synthase (NOS) activity and cGMP content in platelets were analyzed. Moreover, platelet function, plasma levels of L-arginine, metabolic and clinical markers were investigated in these patients and controls.
L-arginine transport (pmol/10(9) cells/min) in platelets via system y(+)L was diminished in obese subjects (20.8±4.7, n=10) and MetS patients (18.4±3.8, n=10) compared to controls (52.3±14.8, n=10). The y(+)L transport system correlated negatively to insulin levels and Homeostasis Model Assessment of Insulin Resistance (HOMA IR) index. No differences in NOS activity and cGMP content were found among the groups. Moreover, plasma levels of L-arginine were not affected by obesity or MetS.
Our study provides the first evidence that obesity and MetS lead to a dysfunction of L-arginine influx, which negatively correlates to insulin resistance. These findings could be a premature marker of future cardiovascular complications during adulthood.
一氧化氮（NO）是一种具有多种生理功能的短寿命气体信使，包括调节血流、血小板黏附和聚集抑制。NO 合酶（NOS）催化阳离子氨基酸 L-精氨酸转化为 L-瓜氨酸和 NO。尽管在过去几十年中肥胖症和代谢综合征（MetS）的患病率不断增加，但发病机制和心血管并发症的确切机制仍不完全清楚。我们研究了肥胖症和 MetS 对青少年血小板中 L-精氨酸-NO-cGMP 途径的影响。
共有 26 名青少年患者（13 名肥胖症患者和 13 名 MetS 患者）和健康志愿者（n=14）参加了这项研究。分析了血小板中 L-精氨酸的转运、NOS 活性和 cGMP 含量。此外，还研究了这些患者和对照组的血小板功能、血浆 L-精氨酸水平、代谢和临床标志物。
与对照组（n=10，52.3±14.8 pmol/10(9) 细胞/min）相比，肥胖组（n=10，20.8±4.7 pmol/10(9) 细胞/min）和 MetS 组（n=10，18.4±3.8 pmol/10(9) 细胞/min）的血小板中 L-精氨酸通过系统 y(+)L 的转运减少。y(+)L 转运系统与胰岛素水平和胰岛素抵抗稳态模型评估（HOMA IR）指数呈负相关。各组间 NOS 活性和 cGMP 含量无差异。此外，肥胖症或 MetS 对血浆 L-精氨酸水平没有影响。
我们的研究首次提供了证据，证明肥胖症和 MetS 导致 L-精氨酸内流功能障碍，这与胰岛素抵抗呈负相关。这些发现可能是成年后患未来心血管并发症的早期标志物。
