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Erschienen in: Basic Research in Cardiology 4/2016

01.07.2016 | Original Contribution

Exercise does not activate the β3 adrenergic receptor–eNOS pathway, but reduces inducible NOS expression to protect the heart of obese diabetic mice

verfasst von: Adrien Kleindienst, Sylvain Battault, Elise Belaidi, Stephane Tanguy, Marie Rosselin, Doria Boulghobra, Gregory Meyer, Sandrine Gayrard, Guillaume Walther, Bernard Geny, Gregory Durand, Olivier Cazorla, Cyril Reboul

Erschienen in: Basic Research in Cardiology | Ausgabe 4/2016

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Abstract

Obesity and diabetes are associated with higher cardiac vulnerability to ischemia–reperfusion (IR). The cardioprotective effect of regular exercise has been attributed to β3-adrenergic receptor (β3AR) stimulation and increased endothelial nitric oxide synthase (eNOS) activation. Here, we evaluated the role of the β3AR–eNOS pathway and NOS isoforms in exercise-induced cardioprotection of C57Bl6 mice fed with high fat and sucrose diet (HFS) for 12 weeks and subjected or not to exercise training during the last 4 weeks (HFS-Ex). HFS animals were more sensitive to in vivo and ex vivo IR injuries than control (normal diet) and HFS-Ex mice. Cardioprotection in HFS-Ex mice was not associated with increased myocardial eNOS activation and NO metabolites storage, possibly due to the β3AR–eNOS pathway functional loss in their heart. Indeed, a selective β3AR agonist (BRL37344) increased eNOS activation and had a protective effect against IR in control, but not in HFS hearts. Moreover, iNOS expression, nitro-oxidative stress (protein s-nitrosylation and nitrotyrosination) and ROS production during early reperfusion were increased in HFS, but not in control mice. Exercise normalized iNOS level and reduced protein s-nitrosylation, nitrotyrosination and ROS production in HFS-Ex hearts during early reperfusion. The iNOS inhibitor 1400 W reduced in vivo infarct size in HFS mice to control levels, supporting the potential role of iNOS normalization in the cardioprotective effects of exercise training in HFS-Ex mice. Although the β3AR–eNOS pathway is defective in the heart of HFS mice, regular exercise can protect their heart against IR by reducing iNOS expression and nitro-oxidative stress.
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Metadaten
Titel
Exercise does not activate the β3 adrenergic receptor–eNOS pathway, but reduces inducible NOS expression to protect the heart of obese diabetic mice
verfasst von
Adrien Kleindienst
Sylvain Battault
Elise Belaidi
Stephane Tanguy
Marie Rosselin
Doria Boulghobra
Gregory Meyer
Sandrine Gayrard
Guillaume Walther
Bernard Geny
Gregory Durand
Olivier Cazorla
Cyril Reboul
Publikationsdatum
01.07.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Basic Research in Cardiology / Ausgabe 4/2016
Print ISSN: 0300-8428
Elektronische ISSN: 1435-1803
DOI
https://doi.org/10.1007/s00395-016-0559-0

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