1. β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger
- Author
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Phillippe Obert, Julien Boissiere, Stéphane Nottin, Anne Sophie Polge, Sandrine Gayrard, Gregory Doucende, Cyril Reboul, Aurélie Goux, Patrice Faure, Stéphane Tanguy, Damien Vitiello, Laboratoire de bioénergétique fondamentale et appliquée (LBFA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des adaptations cardiovasculaires à l'Exercice, Avignon Université (AU), Service de Biochimie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hypoxie et physiopathologies cardiovasculaire et respiratoire, Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Joseph Fourier - Grenoble 1 (UJF)
- Subjects
Male ,Physiology ,myocardial dysfunction ,β-adrenergic pathway ,MESH: Physical Conditioning, Animal ,030204 cardiovascular system & hematology ,medicine.disease_cause ,MESH: Isoproterenol ,MESH: Lipid Peroxidation ,Lipid peroxidation ,Ventricular Dysfunction, Left ,chemistry.chemical_compound ,0302 clinical medicine ,Desensitization (telecommunications) ,MESH: Ventricular Dysfunction, Left ,polycyclic compounds ,MESH: Animals ,MESH: NADPH Oxidase ,MESH: Oxidative Stress ,NADPH oxidase ,biology ,Biochemistry ,cardiovascular system ,Cardiac function curve ,MESH: Troponin I ,medicine.medical_specialty ,MESH: Myocardium ,MESH: Rats ,Heart Ventricles ,MESH: Receptors, Adrenergic, beta ,Contractility ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Physical Conditioning, Animal ,Physiology (medical) ,Internal medicine ,Receptors, Adrenergic, beta ,medicine ,Animals ,Rats, Wistar ,Heart Failure ,Myocardium ,Troponin I ,Isoproterenol ,Acetophenones ,NADPH Oxidases ,MESH: Rats, Wistar ,biochemical phenomena, metabolism, and nutrition ,MESH: Male ,Rats ,Oxidative Stress ,Endocrinology ,chemistry ,MESH: Acetophenones ,MESH: Heart Failure ,Apocynin ,biology.protein ,Lipid Peroxidation ,MESH: Heart Ventricles ,030217 neurology & neurosurgery ,Ex vivo ,Oxidative stress - Abstract
International audience; Prolonged strenuous exercise (PSE) induces transient left ventricular (LV) dysfunction. Previous studies suggest that β-adrenergic pathway desensitization could be involved in this phenomenon, but it remains to be confirmed. Moreover, other underlying mechanisms involving oxidative stress have been recently proposed. The present study aimed to evaluate the involvement of both the β-adrenergic pathway and NADPH oxidase (Nox) enzyme-induced oxidative stress in myocardial dysfunction in rats following PSE. Rats were divided into 4 groups: controls (Ctrl), 4-h exercised on treadmill (PSE), and 2 groups in which Nox enzyme was inhibited with apocynin treatment (Ctrl APO and PSE APO, respectively). We evaluated cardiac function in vivo and ex vivo during basal conditions and isoproterenol stress. GSH/GSSG ratio, cardiac troponin I (cTnI) release, and lipid peroxidation (MDA) were evaluated. PSE induced a decrease in LV developed pressure, intrinsic myocardial contractility, and relaxation associated with an increase in plasma cTnI release. Our in vivo and ex vivo results demonstrated no differences in myocardial response to isoproterenol and of effective dose 50 between control and PSE rats. Interestingly, the LV dysfunction was reversed by apocynin treatment. Moreover, apocynin prevented cellular oxidation [GSH/GSSG ratio: PSE APO rats vs. PSE rats in arbitrary units (au): 1.98 ± 0.07 vs. 1.35 ± 0.10; P < 0.001]. However, no differences in MDA were observed between groups. These data suggest that myocardial dysfunction observed after PSE was not due to β-adrenergic receptor desensitization but could be due to a signaling oxidative stress from the Nox enzyme.
- Published
- 2011