Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training

Author(s):Show less -

Bacurau, Aline V. N. ; Jardim, Maira A. ; Ferreira, Julio C. B. ; Bechara, Luiz R. G. ; Bueno, Jr., Carlos R. ; Alba-Loureiro, Tatiana C. ^[1] ; Negrao, Carlos E. ^[2] ; Casarini, Dulce E. ^[3] ; Curi, Rui ^[1] ; Ramires, Paulo R. ; Moriscot, Anselmo S. ^[4] ; Brum, Patricia C. ^[5]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Med, Div Nephrol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, BR-05508900 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Dept Biodinam Movimento Corpo Humano, Escola Educacao Fis & Esporte, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: Journal of Applied Physiology; v. 106, n. 5, p. 1631-1640, MAY 2009.
• Web of Science Citations: 59

Abstract

Bacurau AV, Jardim MA, Ferreira JC, Bechara LR, Bueno CR Jr, Alba-Loureiro TC, Negrao CE, Casarini DE, Curi R, Ramires PR, Moriscot AS, Brum PC. Sympathetic hyperactivity differentially affects skeletal muscle mass in developing heart failure: role of exercise training. J Appl Physiol 106: 1631-1640, 2009. First published January 29, 2009; doi:10.1152/japplphysiol.91067.2008.-Sympathetic hyperactivity (SH) is a hallmark of heart failure (HF), and several lines of evidence suggest that SH contributes to HF-induced skeletal myopathy. However, little is known about the influence of SH on skeletal muscle morphology and metabolism in a setting of developing HF, taking into consideration muscles with different fiber compositions. The contribution of SH on exercise tolerance and skeletal muscle morphology and biochemistry was investigated in 3- and 7-mo-old mice lacking both alpha(2A)- and alpha(2C)-adrenergic receptor subtypes (alpha(2A)/alpha(2C)ARKO mice) that present SH with evidence of HF by 7 mo. To verify whether exercise training (ET) would prevent skeletal muscle myopathy in advanced-stage HF, alpha(2A)/alpha(2C)ARKO mice were exercised from 5 to 7 mo of age. At 3 mo, alpha(2A)/alpha(2C)ARKO mice showed no signs of HF and preserved exercise tolerance and muscular norepinephrine with no changes in soleus morphology. In contrast, plantaris muscle of alpha(2A)/alpha(2C)ARKO mice displayed hypertrophy and fiber type shift (IIA -> IIX) paralleled by capillary rarefaction, increased hexokinase activity, and oxidative stress. At 7 mo, alpha(2A)/alpha(2C)ARKO mice displayed exercise intolerance and increased muscular norepinephrine, muscular atrophy, capillary rarefaction, and increased oxidative stress. ET reestablished alpha(2A)/alpha(2C)ARKO mouse exercise tolerance to 7-mo-old wild-type levels and prevented muscular atrophy and capillary rarefaction associated with reduced oxidative stress. Collectively, these data provide direct evidence that SH is a major factor contributing to skeletal muscle morphological changes in a setting of developing HF. ET prevented skeletal muscle myopathy in alpha(2A)/alpha(2C)ARKO mice, which highlights its importance as a therapeutic tool for HF. (AU)

• FAPESP's process: 06/56321-6 - Involvement of protein kinase C βII and ε isoforms in heart failure induced by myocardial infarction
• Grantee: Julio Cesar Batista Ferreira
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 05/59740-7 - Physical exercise and autonomic control in cardiovascular physiopathology
• Grantee: Carlos Eduardo Negrão
• Support Opportunities: Research Projects - Thematic Grants