Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice

Exercise training delays cardiac dysfunction and prevents calcium handling abnormalities in sympathetic hyperactivity-induced heart failure mice

Author Medeiros, Alessandra Google Scholar
Rolim, Natale P. L. Google Scholar
Oliveira, Rodrigo S. F. Google Scholar
Rosa, Kaleizu T. Google Scholar
Mattos, Katt C. Google Scholar
Casarini, Dulce E. Autor UNIFESP Google Scholar
Irigoyen, Maria Claudia Google Scholar
Krieger, Eduardo M. Google Scholar
Krieger, Jose Eduardo Google Scholar
Negrao, Carlos Eduardo Google Scholar
Brum, Patricia C. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Abstract Exercise training (ET) is a coadjuvant therapy in preventive cardiology. It delays cardiac dysfunction and exercise intolerance in heart failure (HF); however, the molecular mechanisms underlying its cardioprotection are poorly understood. We tested the hypothesis that ET would prevent Ca2+ handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wildtype (WT) and congenic (alpha 2A/alpha 2C)-adrenoceptor knockout ((alpha 2A/alpha 2C)ARKO) mice with C57BL6/J genetic background (3-5 mo of age) were randomly assigned into untrained and exercise-trained groups. ET consisted of 8-wk swimming session, 60 min, 5 days/wk. Fractional shortening (FS) was assessed by two-dimensional guided M-mode echocardiography. the protein expression of ryanodine receptor (RyR), phospho-Ser(2809)-RyR, sarcoplasmic reticulum Ca2+ ATPase (SERCA2), Na+/Ca2+ exchanger (NCX), phospholamban (PLN), phospho-Ser(16)-PLN, and phospho-Thr(17)-PLN were analyzed by Western blotting. At 3 mo of age, no significant difference in FS and exercise tolerance was observed between WT and (alpha 2A/alpha 2C)ARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, (alpha 2A/alpha 2C)ARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, (alpha 2A/alpha 2C)ARKO mice displayed increased phospho-Ser(16)-PLN (76%) and phospho-Ser(2809)-RyR (49%). ET in (alpha 2A/alpha 2C)ARKO mice prevented exercise intolerance, ventricular dysfunction, and decreased plasma norepinephrine. ET significantly increased the expression of SERCA2 (58%) and phospho-Ser(16)-PLN (30%) while it restored the expression of phospho-Ser(2809)-RyR to WT levels. Collectively, we provide evidence that improved net balance of Ca2+ handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.
Keywords calcium handling proteins
ventricular function
plasma norepinephrine levels
exercise conditioning
Language English
Date 2008-01-01
Published in Journal of Applied Physiology. Bethesda: Amer Physiological Soc, v. 104, n. 1, p. 103-109, 2008.
ISSN 8750-7587 (Sherpa/Romeo, impact factor)
Publisher Amer Physiological Soc
Extent 103-109
Origin http://dx.doi.org/10.1152/japplphysiol.00493.2007
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000252398700014
URI http://repositorio.unifesp.br/handle/11600/30239

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