Exercise Protects Against Myocardial Ischemia–Reperfusion Injury via Stimulation of β 3 -Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols
- 10 June 2011
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 108 (12), 1448-1458
- https://doi.org/10.1161/circresaha.111.241117
Abstract
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 β3-adrenergic receptors (β3-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 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. Conclusions: 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 (ie, nitrite and nitrosothiols).Keywords
This publication has 40 references indexed in Scilit:
- Adverse ventricular remodeling and exacerbated NOS uncoupling from pressure-overload in mice lacking the β3-adrenoreceptorJournal of Molecular and Cellular Cardiology, 2009
- Effects of exenatide on circulating glucose, insulin, glucagon, cortisol and catecholamines in healthy volunteers during exerciseDiabetologia, 2009
- Protein S-nitrosylation in health and disease: a current perspectiveTrends in Molecular Medicine, 2009
- Hydrogen Sulfide Mediates Cardioprotection Through Nrf2 SignalingCirculation Research, 2009
- Endothelial nitric oxide synthase phosphorylation in treadmill‐running mice: role of vascular signalling kinasesThe Journal of Physiology, 2009
- Endogenous S -nitrosothiols protect against myocardial injuryProceedings of the National Academy of Sciences of the United States of America, 2009
- AMP-Activated Protein Kinase Is Involved in Endothelial NO Synthase Activation in Response to Shear StressArteriosclerosis, Thrombosis, and Vascular Biology, 2006
- Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the ratThe Journal of Physiology, 2005
- Induction of β3-Adrenergic Receptor Functional Expression following Chronic Stimulation with Noradrenaline in Neonatal Rat CardiomyocytesThe Journal of pharmacology and experimental therapeutics, 2005
- Nitrite is a signaling molecule and regulator of gene expression in mammalian tissuesNature Chemical Biology, 2005