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内皮型一氧化氮合酶基因单倍型与运动后心血管自主神经调节功能的恢复间接相关。

eNOS gene haplotype is indirectly associated with the recovery of cardiovascular autonomic modulation from exercise.

作者信息

Silva Bruno M, Barbosa Thales C, Neves Fabricia J, Sales Allan K, Rocha Natalia G, Medeiros Renata F, Pereira Felipe S, Garcia Vinicius P, Cardoso Fabiane T, Nobrega Antonio C L

机构信息

Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil; Department of Physiology, Section of Exercise Physiology, Federal University of São Paulo, São Paulo, Brazil.

Laboratory of Exercise Sciences, Department of Physiology and Pharmacology, Fluminense Federal University, Niterói, Rio de Janeiro, Brazil.

出版信息

Auton Neurosci. 2014 Dec;186:77-84. doi: 10.1016/j.autneu.2014.09.001. Epub 2014 Sep 9.

DOI:10.1016/j.autneu.2014.09.001
PMID:25242530
Abstract

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene decrease expression and activation of eNOS in vitro, which is associated with lower post-exercise increase in vasodilator reactivity in vivo. However, it is unknown whether such polymorphisms are associated with other eNOS-related phenotypes during recovery from exercise. Therefore, we investigated the impact of an eNOS haplotype containing polymorphic alleles at loci -786 and 894 on the recovery of cardiovascular autonomic function from exercise. Sedentary, non-obese, healthy subjects were enrolled [n = 107, age 32 ± 1 years (mean ± SEM)]. Resting autonomic modulation (heart rate variability, systolic blood pressure variability, and spontaneous baroreflex sensitivity) and vascular reactivity (forearm hyperemic response post-ischemia) were assessed at baseline, 10, 60, and 120 min after a maximal cardiopulmonary exercise test. Besides, autonomic function was assessed by heart rate recovery (HRR) immediately after peak exercise. Haplotype analysis showed that vagal modulation (i.e., HF n.u.) was significantly higher, combined sympathetic and vagal modulation (i.e., LF/HF) was significantly lower and total blood pressure variability was significantly lower post-exercise in a haplotype containing polymorphic alleles (H2) compared to a haplotype with wild type alleles (H1). HRR was similar between groups. Corroborating previous evidence, H2 had significantly lower post-exercise increase in vasodilator reactivity than H1. In conclusion, a haplotype containing polymorphic alleles at loci -786 and 894 had enhanced recovery of autonomic modulation from exercise, along with unchanged HRR, and attenuated vasodilator reactivity. Then, these results suggest an autonomic compensatory response of a direct deleterious effect of eNOS polymorphisms on the vascular function.

摘要

内皮型一氧化氮合酶(eNOS)基因多态性在体外会降低eNOS的表达和活性,这与体内运动后血管舒张反应性的较低增加有关。然而,尚不清楚此类多态性是否与运动恢复过程中其他与eNOS相关的表型有关。因此,我们研究了一个在-786和894位点含有多态性等位基因的eNOS单倍型对运动后心血管自主功能恢复的影响。招募久坐不动、非肥胖的健康受试者[n = 107,年龄32±1岁(平均值±标准误)]。在最大心肺运动试验后的基线、10、60和120分钟,评估静息自主调节(心率变异性、收缩压变异性和自发性压力反射敏感性)和血管反应性(缺血后前臂充血反应)。此外,在运动峰值后立即通过心率恢复(HRR)评估自主功能。单倍型分析显示,与含有野生型等位基因的单倍型(H1)相比,在含有多态性等位基因的单倍型(H2)中,运动后迷走神经调节(即高频标准化单位)显著更高,交感神经和迷走神经联合调节(即低频/高频)显著更低,总血压变异性显著更低。两组之间的HRR相似。与先前的证据一致,H2运动后血管舒张反应性的增加显著低于H1。总之,一个在-786和894位点含有多态性等位基因的单倍型具有增强的运动后自主调节恢复能力,同时HRR不变,且血管舒张反应性减弱。因此,这些结果提示了eNOS多态性对血管功能直接有害作用的自主代偿反应。

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