Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease
Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease
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DOI：
10.1161/01.cir.0000154560.88933.7e
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发表时间：
2005-02-08
期刊：
影响因子：
37.8
通讯作者：
Hambrecht, R
中科院分区：
文献类型：
--
作者：
Adams, V;Linke, A;Hambrecht, R
背景-在稳定型冠心病患者中，体育锻炼（ET）可改善内皮功能障碍.介导增强的血管功能的潜在机制是活性氧（ROS）对内皮源性一氧化氮的分解减少。本研究的目的是分析ET对有症状的冠状动脉疾病患者左乳内动脉中ROS生成来源的影响。方法和结果-在旁路手术期间从45名患者随机分为训练组（n = 22）或非活动对照组（n = 23）的左乳内动脉环中取样，测定NAD（P）H氧化酶亚基mRNA表达、NAD（P）H氧化酶活性和ROS产生。此外，还测定了内皮功能、血管紧张素II（Ang II）1型和2型受体（AT（1）- R和AT（2）- R）的表达以及Ang II介导的血管收缩。ET导致gp 91（phox）（23.1 +/- 0.5 vs 69.1 +/- 18.1任意单位，训练vs对照）、p22（phox）（0.7 +/- 0.3 vs 2.0 +/- 0.5任意单位）和Nox 4（2.7 +/- 1.2 vs 5.4 +/- 1.0任意单位）的表达显著降低。与对照组相比，训练组的酶活性（2.1 +/- 0.3 vs 4.9 +/- 0.4 mU/ mg）和ROS生成（0.02 +/- 0.01 vs 0.06 +/- 0.02任意单位）显著降低。在功能水平上，ET可改善乙酰胆碱介导的血管舒张作用，使Ang II诱导的血管收缩减少49%，并伴有AT（1）- R降低。（3.7 +/- 0.8对比16.6 +/- 5.7任意单位，训练组与对照组相比）和AT（2）- R升高（7.8 +/- 2.5 vs 1.6 +/- 0.7任意单位）mRNA表达。结论- ET降低血管NAD（P）H氧化酶和AT（1）- R的表达，导致局部ROS产生减少。这些分子效应在降低的Ang II介导的血管收缩中会聚。
Background - In patients with stable coronary artery disease, physical exercise training ( ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium- derived nitric oxide by reactive oxygen species ( ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease.Methods and Results - In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training ( n = 22) or an inactive control ( n = 23) group, the mRNA expression of NAD( P) H oxidase subunits, NAD( P) H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II ( Ang II) receptor type 1 and 2 ( AT(1)- R and AT(2)- R), and Ang II- mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91(phox) ( 23.1 +/- 0.5 versus 69.1 +/- 18.1 arbitrary units, training versus control), p22(phox) ( 0.7 +/- 0.3 versus 2.0 +/- 0.5 arbitrary units), and Nox4 ( 2.7 +/- 1.2 versus 5.4 +/- 1.0 arbitrary units). Enzymatic activity ( 2.1 +/- 0.3 versus 4.9 +/- 0.4 mU/ mg) and ROS generation ( 0.02 +/- 0.01 versus 0.06 +/- 0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine- mediated vasodilatation and a 49% reduction in Ang II - induced vasoconstriction, accompanied by lower AT(1)- R ( 3.7 +/- 0.8 versus 16.6 +/- 5.7 arbitrary units, training versus control) and higher AT(2)- R ( 7.8 +/- 2.5 versus 1.6 +/- 0.7 arbitrary units) mRNA expression.Conclusions - ET reduces vascular expression of NAD( P) H oxidase and AT(1)- R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II - mediated vasoconstriction.