Aerobic Exercise Training Lowers Resting Blood Pressure and Attenuates Progression of Muscle Mechano‐reflex Sensitization in Chronic Kidney Disease

Abstract

IntroductionChronic Kidney Disease (CKD) patients exhibit exaggerated blood pressure (BP) reactivity during exercise that is associated with cardiovascular mortality. One mechanism contributing to abnormal neuro‐circulatory responses in CKD is a heightened sensitivity of the muscle mechano‐reflex. Muscle mechanoreceptors have been shown to have pleiotropic properties and can be sensitized by metabolites that accumulate within exercising skeletal muscle in chronic disease states. We hypothesized that 12 weeks of aerobic cycling exercise would reduce resting BP and attenuate BP and muscle sympathetic nerve activity (MSNA) reactivity during muscle mechano‐reflex activation in CKD.Methods30 CKD participants (age=61±2y) were randomized to 12 weeks of aerobic cycling exercise (N=15) for 20–45 min at 80% of heart rate reserve, versus stretching (active control intervention, N=15), 3 days/week. Resting BP was measured in triplicate via oscillometry. To induce metabolite accumulation, participants performed 3‐min of static handgrip (SHG) at 30% of maximal voluntary contraction. Immediately prior to handgrip cessation, a cuff was inflated around the upper arm at suprasystolic levels for 4‐min to trap accumulated metabolites within the muscle. During the final 2‐min of this period, the muscle was passively (PAS) stretched to activate the muscle mechano‐reflex in the setting of metabolite accumulation. BP and MSNA were measured during the final min of SHG and during the 2‐min of PAS, before and following the 12‐week intervention. All data were analyzed via 2‐way repeated measures ANOVAs (group x time) followed by Tukey post‐hoc tests.ResultsResting mean arterial pressure (MAP) tended to decrease in the exercise group (93±2 to 87±2 mmHg from week 0 to week 12, P=0.07) with no change following stretching (97±3 to 95±2 mmHg from week 0 to week 12, P=0.71). There was no difference in MAP reactivity during SHG between groups at baseline (P=0.29). MAP remained elevated from baseline during PAS in both groups, and there was no difference in the magnitude of increase in MAP during PAS from pre‐ vs post‐intervention in the exercise group (Δ MAP+14±2 vs. +15±3 mmHg at week 0 and 12, respectively, P=0.82). Unexpectedly, however, there was an increase in the magnitude of change in MAP during PAS from pre‐ vs post‐intervention in the stretching group (Δ MAP +12±2 vs. +18±3 at week 0 and 12, respectively, P=0.02). MSNA reactivity data collection is ongoing.DiscussionIn support of our hypothesis, 12 weeks of aerobic cycling exercise lowers resting blood pressure in CKD. While we observed no change in BP reactivity during mechano‐reflex activation following exercise training, we observed a heightened BP response during mechano‐reflex activation following stretching. These findings suggest that aerobic exercise training improves blood pressure at rest and attenuates the progression of heightened muscle mechano‐reflex activation in CKD stages III–IV.Support or Funding InformationThis work was supported by R01HL135183 and 1F32HL147547‐01