Exercise protects against myocardial ischemia-reperfusion injury via stimulation of β(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols.
Exercise protects against myocardial ischemia-reperfusion injury via stimulation of β(3)-adrenergic receptors and increased nitric oxide signaling: role of nitrite and nitrosothiols.
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DOI：
10.1161/circresaha.111.241117
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发表时间：
2011-06-10
影响因子：
20.1
通讯作者：
Lefer DJ
中科院分区：
文献类型：
--
作者：
Calvert JW;Condit ME;Aragón JP;Nicholson CK;Moody BF;Hood RL;Sindler AL;Gundewar S;Seals DR;Barouch LA;Lefer DJ
在动物模型中，运动训练可持续保护动物免受缺血再灌注损伤，并与人类心脏病发作后的生存率提高有关。目前尚不清楚运动如何保护心脏，但很明显，内皮型一氧化氮合酶（eNOS）和一氧化氮（NO）发挥作用。为了确定β3-肾上腺素能受体（β3-AR）、eNOS激活和NO代谢产物（亚硝酸盐和亚硝基硫醇）在运动的持续心脏保护作用中的作用，我们在这里表明，自愿运动减少了4周训练期后小鼠的心肌损伤，并且这些保护作用可以在训练停止后持续至少1周。运动的持续心脏保护作用是由eNOS磷酸化状态的改变（丝氨酸1177增加和苏氨酸495减少）介导的，导致心脏中NO产生和NO代谢物（亚硝酸盐和亚硝基硫醇）储存增加。进一步的证据表明，eNOS磷酸化状态和NO产生的改变是由β3-AR刺激介导的，并且在对运动的响应中，β3-AR缺乏导致缺血再灌注损伤后心肌梗死的加重。我们的研究结果清楚地表明，运动通过刺激β3-AR和增加一氧化氮代谢产物（即，亚硝酸盐和亚硝基硫醇）。
Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but it is apparent that endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) play a role. To determine the role of β3-adrenergic receptors (β3-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise Here we show that voluntary exercise reduces myocardial injury in mice following a 4-week training period and that these protective effects can be sustained for at least 1 week following the cessation of the training. The sustained cardioprotective effects of exercise are mediated by alterations in the phosphorylation status of eNOS (increase in serine 1177 and decrease in threonine 495) leading to an increase in NO generation and storage of NO metabolites (nitrite and nitrosothiols) in the heart. Further evidence revealed that the alterations in eNOS phosphorylation status and NO generation were mediated by β3-AR stimulation and that in response to exercise a deficiency of β3-ARs leads to an exacerbation of myocardial infarction following ischemia-reperfusion injury. Our findings clearly demonstrate that exercise protects the heart against myocardial ischemia-reperfusion injury by stimulation of β3-ARs and increased cardiac storage of nitric oxide metabolites (i.e., nitrite and nitrosothiols).