Discussion
vascular dysfunction, CKD, artery stiffness, SNS overactivity, vascular stiffness, heart failure
ADVERSE EVENTS, HEART FAILURE
The present study demonstrates for the first time to our knowledge that exercise training ameliorates worsening of resting SNS overactivity and increased aortic wave reflection associated with vascular stiffness in older sedentary adults with moderate to advanced CKD. This randomized, controlled trial showed that 12 weeks of cycling exercise prevented the progressive increase in resting MSNA and AIx that was observed in the Stretching control group. Furthermore, the magnitude of reduction in MSNA and AIx following exercise training was dependent on baseline levels as well as exercise adherence, with greater reductions observed in participants with higher resting MSNA and AIx, and in those with higher adherence to exercise sessions. Lastly, increased resting MSNA was associated with higher AIx at baseline, suggesting interactive regulation of sympathetic and vascular function in CKD. Our supervised moderate-intensity aerobic exercise intervention was well tolerated with no adverse events and high adherence rates. Although exercise is currently underprescribed in patients with CKD, aerobic exercise training may be a safe and feasible therapeutic intervention to improve autonomic and vascular dysfunction in CKD.Prior literature has shown that exercise training reduces SNS activity in other clinical populations that are also characterized by SNS overactivity. In patients with heart failure (We also observed a positive association between MSNA and AIx at baseline in CKD. Although causal mechanisms underlying this relationship remain unexplored, prior work has shown that sympathetic activation influences short-term alterations in arterial distensibility (Interestingly, we observed that the magnitude of reduction in resting MSNA following exercise training was greater in participants with higher resting MSNA at baseline. Previous evidence suggests that the sympathoinhibitory effect of exercise training may be limited to populations with chronically increased SNS activity, while exercise training exerts no effect on sympathetic regulation in healthy participants (Although exercise training prevented the worsening of AIx observed in the control group, we observed no change in PWV with either intervention. While carotid-to-femoral PWV (c-f PWV) is a measurement of large artery stiffness determined mainly by structural remodeling in central elastic arteries, AIx measures the magnitude of augmented pulse wave reflection during the early systolic phase that is driven by both central large artery stiffness as well as accumulated resistance from small to medium peripheral arteries. These smaller arteries are more densely innervated, potentially leading to greater sympathetic control, as compared with large arteries that predominantly rely on structural elastic properties to dampen high pulsatile flow. To support this concept, renal transplant patients with increased MSNA had reduced distensibility of the muscular (medium-sized) artery, but not the elastic type (large-sized) artery (