Increased superoxide production in hypertensive patients with diabetes mellitus - Role of nitric oxide synthase
Increased superoxide production in hypertensive patients with diabetes mellitus - Role of nitric oxide synthase
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DOI：
10.1016/j.amjhyper.2005.01.004
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发表时间：
2005-06-01
影响因子：
3.2
通讯作者：
McVeigh, GE
中科院分区：
文献类型：
--
作者：
Dixon, LJ;Hughes, SM;McVeigh, GE
背景：高血压和糖尿病是氧化应激增加和心血管风险增加的重要独立危险因素。高血压和糖尿病的结合会导致心血管风险急剧增加。高血压和糖尿病中氧化应激的增强与一氧化氮 (NO) 生物利用度的降低有关，因为它与主要源自 NAD(P)H 依赖性氧化酶的血管超氧化物 (O-2(中心点-)) 相互作用。当与必需辅因子解偶联时，NO 合酶 III (NOS III) 也可以产生 O-2（中心点-）。我们研究了单纯高血压患者和合并糖尿病的患者的血小板超氧化物生成，调查了 NOS III 解偶联对血小板超氧化物生成的贡献。方法和结果：获得凝胶过滤的血小板，并用佛波醇 12-肉豆蔻酸酯 13-乙酸酯刺激，并使用光泽精增强化学发光检测 O-2（中心点-）生成。糖尿病和高血压患者的超氧化物产生量（6.4 +/- 1.6 pmol/min/10(8) 血小板）显着高于高血压患者（1.6 +/- 0.6 pmol/min/10(8) 血小板）（P
Background: Hypertension and diabetes are important independent risk factors for increased oxidative stress and increased cardiovascular risk. The combination of hypertension and diabetes results in a dramatic increase in cardiovascular risk.Enhanced oxidative stress in hypertension and diabetes is linked to decreased nitric oxide (NO) bioavailability because of its interaction with vascular superoxide (O-2(center dot-)), derived predominantly from NAD(P)H-dependent oxidases. When uncoupled from essential cofactors, NO synthase III (NOS III) can also produce O-2(center dot-). We studied platelet superoxide production in patients with hypertension alone and in patients with coexistent diabetes mellitus, investigating the contribution of NOS III uncoupling to platelet superoxide production.Methods and Results: Gel-filtered platelets were obtained and were stimulated with Phorbol 12-myristate 13-acetate, and O-2(center dot-) production was detected using lucigenin-enhanced chemiluminescence. Superoxide production was significantly higher in patients with diabetes and hypertension (6.4 +/- 1.6 pmol/min/10(8) platelets) than in patients with hypertension (1.6 +/- 0.6 pmol/min/10(8) platelets) (P