Exercise Training Can Prevent Cardiac Hypertrophy Induced by Sympathetic Hyperactivity with Modulation of Kallikrein-Kinin Pathway and Angiogenesis

Sympathetic hyperactivity induces adverse effects in myocardial. Recent studies have shown that exercise training induces cardioprotection against sympathetic overload; however, relevant mechanisms of this issue remain unclear. We analyzed whether exercise can prevent pathological hypertrophy induced by sympathetic hyperactivity with modulation of the kallikrein-kinin and angiogenesis pathways. Male Wistar rats were assigned to non-trained group that received vehicle; non-trained isoproterenol treated group (Iso, 0.3 mg kg(-1) day(-1)); and trained group (Iso+Exe) which was subjected to sympathetic hyperactivity with isoproterenol. the Iso rats showed hypertrophy and myocardial dysfunction with reduced force development and relaxation of muscle. the isoproterenol induced severe fibrosis, apoptosis and reduced myocardial capillary. Interestingly, exercise blunted hypertrophy, myocardial dysfunction, fibrosis, apoptosis and capillary decreases. the sympathetic hyperactivity was associated with high abundance of ANF mRNA and beta-MHC mRNA, which was significantly attenuated by exercise. the tissue kallikrein was augmented in the Iso+Exe group, and kinin B-1 receptor mRNA was increased in the Iso group. Moreover, exercise induced an increase of kinin B-2 receptor mRNA in myocardial. the myocardial content of eNOS, VEGF, VEGF receptor 2, pAkt and Bcl-2 were increased in the Iso+Exe group. Likewise, increased expression of pro-apoptotic Bad in the Iso rats was prevented by prior exercise. Our results represent the first demonstration that exercise can modulate kallikrein-kinin and angiogenesis pathways in the myocardial on sympathetic hyperactivity. These findings suggest that kallikrein-kinin and angiogenesis may have a key role in protecting the heart.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)National Council for Scientific and TechnologicalUniv Nove Julho Uninove, Programa Posgrad Ciencias Reabilitacao, São Paulo, BrazilUniversidade Federal de São Paulo Unifesp, São Paulo, BrazilUniv São Paulo, São Paulo, BrazilUniv Nove Julho Uninove, Programa Posgrad Med, São Paulo, BrazilUniversidade Federal de São Paulo Unifesp, São Paulo, BrazilFAPESP: 2009/54225-8National Council for Scientific and Technological: 477458/2009-2National Council for Scientific and Technological: 479395/2012-8Web of Scienc