Therefore, reduced plasma apelin levels may be associated with reductions of NO bioavailability in older adults, and this may in turn result in increased arterial stiffness. Additionally, in patients with type 2 diabetes mellitus, regular exercise training elevates circulating apelin levels, and higher levels of physical activity caused larger increases in apelin levels than lower levels of activity. Furthermore, a study in hypertensive rats showed that exercise training promotes mRNA expression and tissue concentration of apelin in the aorta. However, the association between Danshensu aerobic exercise traininginduced changes in arterial stiffness and circulating apelin level in healthy middle-aged and older Ganoderic-acid-G adults remains unclear. We hypothesized that aerobic exercise training would elevate plasma apelin levels along with plasma NOx levels in middle-aged and older adults, and that this increase in apelin may be participated in endurance exercise training-induced reduction of arterial stiffness. To test our hypothesis, we measured plasma apelin levels, nitrite/nitrate concentrations, and arterial stiffness in middle-aged and older adults using a randomized controlled exercise intervention trial. This study investigated the effects of regular aerobic exercise on apelin concentrations in middle-aged and older adults before and after 8-week aerobic exercise training. After the exercise training intervention, arterial stiffness decreased, concomitantly, plasma apelin levels elevated along with plasma NOx levels. By contrast, there were no significant changes in these parameters in the sedentary control group. Furthermore, the effect of training on carotid b-stiffness was negatively correlated with the effect on plasma apelin levels. Thus, an elevation of plasma apelin levels is associated with a concomitant decrease in arterial stiffness through aerobic exercise training in middle-aged and older adults. Additionally, the effect of training on plasma NOx levels was positively correlated with the effect on plasma apelin levels. 
Several studies have suggested that increases in NO production resulting from endurance exercise training may be a causal factor in reduction of arterial stiffness risks, in both humans and animals. Therefore, these results suggest that arterial NO bioavailability via apelin may be participated in variation of arterial stiffness in middle-aged and older adults. In a previous study, circulating apelin levels were increased by 6 months of aerobic training consisting of walking, treadmill running, cycling, or calisthenics at 60�C70% of maximal heart rate for 60 min, 4 days/week, whereas 8-types of resistance training at 60�C80% of one repetition maximum, 4 days/week, did not change apelin levels in patients with type 2 diabetes mellitus. Patients with higher physical activity had higher plasma apelin levels than less physically physical active patients. In animal studies using hypertensive model rats, 9-week swimming training normalized mRNA expression and tissue concentration of apelin in aorta, along with apelin plasma levels. Previously, however, the effect of regular aerobic exercise on apelin concentration in middle-aged and older adults had remained unclear.