Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation.
Aerobic exercise protects against pressure overload-induced cardiac dysfunction and hypertrophy via β3-AR-nNOS-NO activation.
复制标题
有氧运动通过 β3-AR-nNOS-NO 激活防止压力超负荷引起的心脏功能障碍和肥厚
DOI：
10.1371/journal.pone.0179648
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Niu X
中科院分区：
文献类型：
--
作者：
Wang B;Xu M;Li W;Li X;Zheng Q;Niu X
有氧运动可持续预防心脏肥大和心力衰竭（HF）。一氧化氮合酶（NOS）和一氧化氮（NO）在运动介导的心肌保护中发挥重要作用，但运动中NOS/NO的激活机制尚不清楚。本研究的目的是确定β3-肾上腺素能受体（β3-ARs）、NOS激活和NO代谢产物（亚硝酸盐和亚硝基硫醇）在有氧运动的持续心脏保护作用中的作用。采用主动脉缩窄术（TAC）建立HF模型。动物通过游泳进行中等有氧运动9周和/或在TAC手术后1天以0.1 mg/kg/h的β3-AR特异性抑制剂SR 59230 A处理。采用Masson三色染色、FITC标记麦胚凝集素染色、酶联免疫吸附试验（ELISA）和超声心动图分别检测心肌纤维化、心肌细胞大小、血浆儿茶酚胺（CA）水平、心功能和几何形态。Western blot分析目的蛋白的表达。硝酸还原酶法测定心肌NO生成量。检测心肌超氧化物歧化酶（SOD）、丙二醛（MDA）和活性氧（ROS）的含量，评价心肌氧化应激。有氧运动训练改善了TAC小鼠扩张的左心室功能，部分减轻了心脏肥大和纤维化的程度。有氧运动后，TAC小鼠β3-AR表达增加，神经元型NOS（nNOS）活性增强，NO生成增加。而SR 59230 A选择性抑制β3-AR则可抑制nNOS诱导的NO生成。此外，有氧运动训练降低心肌ROS和MDA含量，增加心肌SOD水平，这两种作用都被SR 59230 A部分减弱。本研究提示有氧运动训练可改善心衰小鼠心脏收缩功能，减轻心衰小鼠左室扩张、心肌纤维化和肥厚。有氧运动的保护作用机制与β3-AR-nNOS-NO通路的激活有关。
Aerobic exercise confers sustainable protection against cardiac hypertrophy and heart failure (HF). Nitric oxide synthase (NOS) and nitric oxide (NO) are known to play an important role in exercise-mediated cardioprotection, but the mechanism of NOS/NO stimulation during exercise remains unclear. The aim of this study is to determine the role of β3-adrenergic receptors (β3-ARs), NOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of aerobic exercise. An HF model was constructed by transverse aortic constriction (TAC). Animals were treated with either moderate aerobic exercise by swimming for 9 weeks and/or the β3-AR-specific inhibitor SR59230A at 0.1 mg/kg/hour one day after TAC operation. Myocardial fibrosis, myocyte size, plasma catecholamine (CA) level, cardiac function and geometry were assessed using Masson’s trichrome staining, FITC-labeled wheat germ agglutinin staining, enzyme-linked immuno sorbent assay (ELISA) and echocardiography, respectively. Western blot analysis was performed to elucidate the expression of target proteins. The concentration of myocardial NO production was evaluated using the nitrate reductase method. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD), malonyldialdehyde (MDA), and reactive oxygen species (ROS). Aerobic exercise training improved dilated left ventricular function and partially attenuated the degree of cardiac hypertrophy and fibrosis in TAC mice. Moreover, the increased expression of β3-AR, activation of neuronal NOS (nNOS), and production of NO were detected after aerobic exercise training in TAC mice. However, selective inhibition of β3-AR by SR59230A abolished the upregulation and activation of nNOS induced NO production. Furthermore, aerobic exercise training decreased the myocardial ROS and MDA contents and increased myocardial levels of SOD; both effects were partially attenuated by SR59230A. Our study suggested that aerobic exercise training could improve cardiac systolic function and alleviate LV chamber dilation, cardiac fibrosis and hypertrophy in HF mice. The mechanism responsible for the protective effects of aerobic exercise is associated with the activation of the β3-AR-nNOS-NO pathway.
影响因子：
2.5
作者：
Mishra OP;Ashraf QM;Delivoria-Papadopoulos M
通讯作者：
Delivoria-Papadopoulos M