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 β-MHC
mRNA, which was significantly attenuated by exercise. The
tissue kallikrein was augmented in the Iso+Exe group, and
kinin B1 receptor
mRNA was increased in the Iso group. Moreover, exercise induced an increase of
kinin B2 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.