Cardioprotection and neurobehavioral impact of swimming training in ovariectomized rats

Abstract

Cardiovascular (CV) disease is the major cause of mortality. Estrogens (E) exert multiple CV and neuroprotective effects. During menopause CV and cognitive pathologies increase dramatically. At present, it is known that E exert many of their beneficial effects through the G protein-coupled estrogen receptor (GPER). Exercise reduces the risk of developing CV diseases. Sodium/proton exchanger (NHE-1) is overexpressed in ovariectomized (OVX) rats, probably due by the increase in reactive oxidative species (ROS). Insulin-like growth factor 1 (IGF-1), the main humoral mediator of exercise, inhibits the NHE-1. We aim to explore the subcellular mechanisms involved in the heart and brain impact of physiological exercise in OVX rats. We speculate that physical training, via IGF-1, prevents the increase in ROS; improving heart and brain physiological functions during menopause. Exercise diminished cardiac ROS production and increased catalase (CAT) activity in OVX rats. In concordance, IGF-1 treatment reduces brain ROS, surely contributing to the improvement in brain behavior. Moreover, aerobic routine was able to prevent, and IGF-1 therapy to revert, NHE-1 hyperactivity in OVX rats. Finally, our results confirm the proposed signaling pathway as: IGF-1/PI3K-AKT/NO. Surprisingly, GPER inhibitor (G36) was able to abolish IGF-1 effect, suggesting that directly or indirectly GPER is part of IGF-1 pathway. We propose that IGF-1 is the main responsible for the protective effect of aerobic training both in heart and brain in OVX rats. Moreover, we showed that not only it is possible to prevent, but also to revert the menopause-induced NHE-1 hyperactivity by exercise/IGF-1 cascade.