Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise.
Neuronal nitric oxide synthase is indispensable for the cardiac adaptive effects of exercise.
复制标题
DOI：
10.1007/s00395-013-0332-6
复制
发表时间：
2013-03
影响因子：
9.5
通讯作者：
Ziolo MT
中科院分区：
文献类型：
--
作者：
Roof SR;Tang L;Ostler JE;Periasamy M;Györke S;Billman GE;Ziolo MT
运动导致心脏的有益适应，这可以在心室肌细胞水平直接观察到。然而，负责这些适应的分子机制还没有得到很好的理解。有趣的是，通过肌细胞内的神经元型一氧化氮合酶（NOS1）的信号传导产生与运动相似的效果。因此，本研究的目的是确定NOS1在运动诱导的心肌细胞有益收缩效应中的作用。经过8周的有氧间歇训练计划，运动训练（Ex）小鼠具有较高的VO2max和心脏肥大相比，久坐（Sed）小鼠。与Sed小鼠的心肌细胞相比，Ex小鼠的心室肌细胞的NOS 1表达和一氧化氮产生增加。值得注意的是，急性NOS1抑制正常化增强收缩（缩短和Ca2+瞬变）在前肌细胞Sed水平。NOS1对收缩的作用是通过增加受磷蛋白磷酸化引起的更大的Ca2+循环介导的。有趣的是，对NOS1敲除小鼠进行类似的有氧间歇训练计划未能产生任何有益的心脏适应（VO2max，肥大和收缩）。这些数据表明，运动训练后观察到的有益心脏适应是通过增强的NOS 1信号传导介导的。因此，增加NOS1信号传导的干预措施可能会模仿运动的有益效果。这一通路可能为不能或不愿运动的心脏病患者提供一个潜在的新的治疗靶点。
Exercise results in beneficial adaptations of the heart that can be directly observed at the ventricular myocyte level. However, the molecular mechanism(s) responsible for these adaptations are not well understood. Interestingly, signaling via neuronal nitric oxide synthase (NOS1) within myocytes results in similar effects as exercise. Thus, the objective was to define the role NOS1 plays in the exercise-induced beneficial contractile effects in myocytes. After an 8 week aerobic interval training program, exercise-trained (Ex) mice had higher VO2max and cardiac hypertrophy compared to sedentary (Sed) mice. Ventricular myocytes from Ex mice had increased NOS1 expression and nitric oxide production compared to myocytes from Sed mice. Remarkably, acute NOS1 inhibition normalized the enhanced contraction (shortening and Ca2+ transients) in Ex myocytes to Sed levels. The NOS1 effect on contraction was mediated via greater Ca2+cycling that resulted from increased phospholamban phosphorylation. Intriguingly, a similar aerobic interval training program on NOS1 knockout mice failed to produce any beneficial cardiac adaptations (VO2max, hypertrophy, and contraction). These data demonstrate that the beneficial cardiac adaptations observed after exercise training were mediated via enhanced NOS1 signaling. Therefore, it is likely that beneficial effects of exercise may be mimicked by the interventions that increase NOS1 signaling. This pathway may provide a potential novel therapeutic target in cardiac patients who are unable or unwilling to exercise.
登录
查看更多内容
影响因子：
5.5
作者：
Copp, Steven W.;Hirai, Daniel M.;Poole, David C.
通讯作者：
Poole, David C.
影响因子：
10.8
作者：
Kemi, OJ;Haram, PM;Ellingsen, O
通讯作者：
Ellingsen, O
DOI：
10.1152/ajpheart.01278.2008
发表时间：
2009-07-01
影响因子：
4.8
作者：
Kavazis, Andreas N.;Alvarez, Sophie;Powers, Scott K.
通讯作者：
Powers, Scott K.
DOI：
10.1097/00005768-200001000-00012
发表时间：
2000-01-01
期刊：
MEDICINE AND SCIENCE IN SPORTS AND EXERCISE
影响因子：
--
作者：
Bassett, DR;Howley, ET
通讯作者：
Howley, ET
DOI：
10.1073/pnas.0404136101
发表时间：
2004-11-09
影响因子：
11.1
作者：
Khan, SA;Lee, K;Hare, JM
通讯作者：
Hare, JM