Exercise Protects Against Myocardial Ischemia-Reperfusion Injury via Stimulation of β3-Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols

被引：170

作者：

Calvert, John W. ^{[1
]}

Condit, Marah E. ^{[1
]}

Aragon, Juan Pablo ^{[1
]}

Nicholson, Chad K. ^{[1
]}

Moody, Bridgette F. ^{[1
]}

Hood, Rebecca L. ^{[1
]}

Sindler, Amy L.

Gundewar, Susheel ^{[1
]}

Seals, Douglas R. ^{[2
]}

Barouch, Lili A. ^{[3
]}

Lefer, David J. ^{[1
]}

机构：

[1] Emory Univ, Dept Surg, Div Cardiothorac Surg, Sch Med,Carlyle Fraser Heart Ctr, Atlanta, GA 30308 USA

[2] Univ Colorado, Dept Integrat Physiol, Boulder, CO 80309 USA

[3] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA

来源：

CIRCULATION RESEARCH | 2011年 / 108卷 / 12期

基金：

美国国家卫生研究院;

关键词：

beta(3)-adrenergic receptor; nitric oxide; cardioprotection; exercise; nitrite; nitrosothiol; S-NITROSYLATION; CARDIOPROTECTION; SYNTHASE; EXPRESSION; PHOSPHORYLATION; RELAXATION; ACTIVATION; REGULATOR; HEALTH; ARTERY;

D O I：

10.1161/CIRCRESAHA.111.241117

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Rationale: 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. Objective: To determine the role of beta(3)-adrenergic receptors (beta(3)-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise. Methods and Results: 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 beta(3)-AR stimulation and that in response to exercise a deficiency of beta(3)-ARs leads to an exacerbation of myocardial infarction following ischemia-reperfusion injury. Conclusions: Our findings clearly demonstrate that exercise protects the heart against myocardial ischemia-reperfusion injury by stimulation of beta(3)-ARs and increased cardiac storage of nitric oxide metabolites (ie, nitrite and nitrosothiols). (Circ Res. 2011;108:1448-1458.)

引用

页码：1448 / U125

页数：23

共 43 条

[1] Alterations of β3-adrenoceptors expression and their myocardial functional effects in physiological model of chronic exercise-induced cardiac hypertrophy [J].