title: β-Adrenergic receptors desensitization is not involved in exercise-induced cardiac fatigue: NADPH oxidase-induced oxidative stress as a new trigger.
abstract: 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.
authors: Laboratory of Cardiovascular Adjustments to Exercise, Univ. of Avignon, 33 Rue Louis Pasteur, 84000 Avignon, France. damien.vitiello@univ-avignon.fr
authors: Damien
authors: D
authors: Vitiello
authors: Julien
authors: J
authors: Boissière
authors: Grégory
authors: G
authors: Doucende
authors: Sandrine
authors: S
authors: Gayrard
authors: Anne
authors: A
authors: Polge
authors: Patrice
authors: P
authors: Faure
authors: Aurélie
authors: A
authors: Goux
authors: Stéphane
authors: S
authors: Tanguy
authors: Philippe
authors: P
authors: Obert
authors: Cyril
authors: C
authors: Reboul
authors: Stéphane
authors: S
authors: Nottin
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000818:Animals; D006333:Heart Failure / Q000378:metabolism* / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D019210:Troponin I / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology
chemical_list: D000098:Acetophenones; D011943:Receptors, Adrenergic, beta; D019210:Troponin I; C056165:acetovanillone; D019255:NADPH Oxidases; D007545:Isoproterenol