Effect of exercise training and carvedilol treatment on cardiac function and structure in mice with sympathetic hyperactivity-induced heart failure

Autor(es)

Medeiros, A. ^[1] ; Vanzelli, A. S. ^[1] ; Rosa, K. T. ^[2] ; Irigoyen, M. C. ^[2] ; Brum, P. C. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Escola Educ Fis & Esporte, Dept Biodinam Movimento Corpo Humano, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Fac Med, Inst Coracao, BR-05508900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Brazilian Journal of Medical and Biological Research; v. 41, n. 9, p. 812-817, SEP 2008.
• Citações Web of Science: 12

Resumo

The present investigation was undertaken to study the effect of β-blockers and exercise training on cardiac structure and function, respectively, as well as overall functional capacity in a genetic model of sympathetic hyperactivity-induced heart failure in mice (α2A/α2CArKO). α2A/α2CArKO and their wild-type controls were studied for 2 months, from 3 to 5 months of age. Mice were randomly assigned to control (N = 45), carvedilol-treated (N = 29) or exercise-trained (N = 33) groups. Eight weeks of carvedilol treatment (38 mg/kg per day by gavage) or exercise training (swimming sessions of 60 min, 5 days/week) were performed. Exercise capacity was estimated using a graded treadmill protocol and HR was measured by tail cuff. Fractional shortening was evaluated by echocardiography. Cardiac structure and gastrocnemius capillary density were evaluated by light microscopy. At 3 months of age, no significant difference in fractional shortening or exercise capacity was observed between wild-type and α2A/α2CArKO mice. At 5 months of age, all α2A/α2CArKO mice displayed exercise intolerance and baseline tachycardia associated with reduced fractional shortening and gastrocnemius capillary rarefaction. In addition, α2A/ α2CArKO mice presented cardiac myocyte hypertrophy and ventricular fibrosis. Exercise training and carvedilol similarly improved fractional shortening in α2A/α2CArKO mice. The effect of exercise training was mainly associated with improved exercise tolerance and increased gastrocnemius capillary density while β-blocker therapy reduced cardiac myocyte dimension and ventricular collagen to wild-type control levels. Taken together, these data provide direct evidence for the respective beneficial effects of exercise training and carvedilol in α2A/α2CArKO mice preventing cardiac dysfunction. The different mechanisms associated with beneficial effects of exercise training and carvedilol suggest future studies associating both therapies. (AU)

• Processo FAPESP: 02/04588-8 - Efeito do treinamento físico na cardiomiopatia induzida por hiperatividade simpática em camundongos knockout para os receptores alfa 2a e alfa 2a e alfa 2c adrenérgicos
• Beneficiário: Patricia Chakur Brum
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 04/00745-7 - Efeito do treinamento físico na cardiomiopatia induzida por hiperatividade simpática em camundongos nocaute para os receptores alfa 2A/alfa 2C-adrenérgicos
• Beneficiário: Alessandra Medeiros
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto