In:
Journal of Applied Physiology, American Physiological Society, Vol. 104, No. 1 ( 2008-01), p. 103-109
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 Ca 2+ handling abnormalities and ventricular dysfunction in sympathetic hyperactivity-induced HF mice. A cohort of male wild-type (WT) and congenic α 2A /α 2C -adrenoceptor knockout (α 2A /α 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 Ca 2+ ATPase (SERCA2), Na + /Ca 2+ 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 α 2A /α 2C ARKO mice. At 5 mo, when cardiac dysfunction is associated with lung edema and increased plasma norepinephrine levels, α 2A /α 2C ARKO mice presented reduced FS paralleled by decreased SERCA2 (26%) and NCX (34%). Conversely, α 2A /α 2C ARKO mice displayed increased phospho-Ser 16 -PLN (76%) and phospho-Ser 2809 -RyR (49%). ET in α 2A /α 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 Ca 2+ handling proteins paralleled by a decreased sympathetic activity on ET are, at least in part, compensatory mechanisms against deteriorating ventricular function in HF.
Type of Medium:
Online Resource
ISSN:
8750-7587
,
1522-1601
DOI:
10.1152/japplphysiol.00493.2007
Language:
English
Publisher:
American Physiological Society
Publication Date:
2008
detail.hit.zdb_id:
1404365-8
SSG:
12
SSG:
31
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