Combination of exercise training and L-arginine reverses aging process through suppression of oxidative stress, inflammation, and apoptosis in the rat heart

Aging-induced progressive decline of molecular and metabolic factors in the myocardium is suggested to be related with heart
dysfunction and cardiovascular disease. Therefore, we evaluated the effects of exercise training and L-arginine supplementation on
oxidative stress, inflammation, and apoptosis in ventricle of the aging rat heart. Twenty-four 24-month-agedWistar rats were randomly
divided into four groups: the aged control, aged exercise, aged L-arginine (orally administered with 150 mg/kg for 12 weeks), and aged
exercise + L-arginine groups. Six 4-month-old rats were also considered the young control. Animals with training program performed
exercise on a treadmill 5 days/week for 12 weeks. After 12 weeks, protein levels of Bax, Bcl-2, pro-caspase-3/cleaved caspase-3,
cytochrome C, and heat shock protein (HSP)-70 were assessed. Tissue contents of total anti-oxidant capacity, superoxide dismutase,
catalase, and levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, and IL-6 were analyzed. Histological and fibrotic
changes were also evaluated. Treadmill exercise and L-arginine supplementation significantly alleviated aging-induced apoptosis with
enhancing HSP-70 expression, increasing anti-oxidant enzyme activity, and suppressing inflammatory markers in the cardiac
myocytes. Potent attenuation in apoptosis, inflammation, and oxidative stress was indicated in the rats with the combination of L-
arginine supplementation and exercise program in comparison with each group (p < 0.05). In addition, fibrosis percentage and collagen
accumulation were significantly lower in the rats with the combination treatment of L-arginine and exercise (p < 0.05). Treadmill
exercise and L-arginine supplementation provided protection against age-induced increase in the myocyte loss and formation of fibrosis
in the ventricle through potent suppression of oxidative stress, inflammations, and apoptosis pathways.