Laboratory of Cardiovascular Physiology and Exercise Science, University of São Paulo State, Rio Claro, São Paulo, Brazil; and.
Laboratory of Molecular Evolution, Institute of Bioscience, University of São Paulo State, Rio Claro, São Paulo, Brazil.
Am J Physiol Heart Circ Physiol. 2014 Jun 15;306(12):H1679-91. doi: 10.1152/ajpheart.00844.2013. Epub 2014 Apr 18.
The number of studies that have evaluated exercise training (ET) and nitric oxide synthase (NOS)3 gene polymorphisms is scarce. The present study was designed to evaluate the relationship between exercise training and NOS3 polymorphisms at -786T>C, 894G>T, and intron 4b/a on blood pressure (BP) using 24-h ambulatory BP monitoring (ABPM), nitrate/nitrite levels (NOx), and redox state. Eighty-six volunteers (51 ± 0.6 yr old) were genotyped into nonpolymorphic and polymorphic groups for each of the three positions of NOS3 polymorphisms. Auscultatory BP, ABPM, SOD activity, catalase activity, NOx levels, and malondialdehyde levels were measured. DNA was extracted from leukocytes, and PCR followed by sequencing was applied for genotype analysis. Aerobic ET consisted of 24 sessions for 3 days/wk for 40 min at moderate intensity. This study was performed in a double-blind and crossover format. ET was effective in lowering office BP (systolic BP: 3.2% and diastolic BP: 3%) as well as ABPM (systolic BP: 2% and diastolic BP: 1.3%). Increased SOD and catalase activity (42.6% and 15.1%, respectively) were also observed. The NOS3 polymorphism for intron 4 mitigated the beneficial effect of ET for systolic BP (nonpolymorphic group: -3.0% and polymorphic group: -0.6%) and diastolic BP (nonpolymorphic group: -3.2% and polymorphic group: -0.5%), but it was not associated with NOx level and redox state. Paradoxical responses were found for positions T786-C and G894T for the NOS3 gene. Consistently, the presence of the polymorphism for intron 4 blunted the beneficial effects of ET in middle-aged adults. Possibly, this effect might be as consequence of intron 4 acting as a short intronic repeat RNA controlling endothelial NOS activity epigenetically.
评估运动训练（ET）和一氧化氮合酶（NOS）3 基因多态性的研究数量很少。本研究旨在通过 24 小时动态血压监测（ABPM）、硝酸盐/亚硝酸盐水平（NOx）和氧化还原状态评估运动训练与 NOS3 基因-786T>C、894G>T 和内含子 4b/a 多态性之间的关系。86 名志愿者（51±0.6 岁）分为每个 NOS3 多态性三个位置的非多态性和多态性组。测量了听诊血压、ABPM、SOD 活性、CAT 活性、NOx 水平和丙二醛水平。从白细胞中提取 DNA，应用 PCR 测序进行基因型分析。有氧运动训练由 24 次，每次 40 分钟，每周 3 天，中等强度组成。该研究采用双盲交叉设计进行。ET 有效降低了诊室血压（收缩压：3.2%，舒张压：3%）和 ABPM（收缩压：2%，舒张压：1.3%）。还观察到 SOD 和 CAT 活性增加（分别为 42.6%和 15.1%）。NOS3 内含子 4 多态性减轻了 ET 对收缩压（非多态性组：-3.0%，多态性组：-0.6%）和舒张压（非多态性组：-3.2%，多态性组：-0.5%）的有益作用，但与 NOx 水平和氧化还原状态无关。NOS3 基因的 T786-C 和 G894T 位置出现了矛盾的反应。一致地，内含子 4 多态性削弱了 ET 在中年成年人中的有益作用。可能，这种效应可能是由于内含子 4 作为短内含子重复 RNA 从表观遗传上控制内皮一氧化氮合酶活性。
