The Effect of Aerobic Exercise Training on Functional Sympatholysis in Patients with Chronic Kidney Disease

Abstract

Intro: Patients with chronic kidney disease (CKD) experience exercise intolerance that is associated with increased risk of cardiovascular disease and poor quality of life. Sympathetic vasoconstriction is markedly blunted during exercise to optimize blood flow to the metabolically active muscles, termed functional sympatholysis. Impaired functional sympatholysis is observed in models with cardiovascular disease and is suggested to contribute to exercise intolerance by limiting adequate muscle blood flow and tissue oxygen delivery to the exercising muscles. Chronic endurance exercise training is known to alter sympathetic regulation of muscle blood flow. Therefore, we investigated the hypotheses that 1) functional sympatholysis is impaired in CKD patients and 2) an aerobic exercise training alters functional sympatholysis status in CKD patents. Method: 79 sedentary individuals with CKD stages III-IV(62±9 yr, 94% hypertensive) and 21 age-matched controls (59±7 yr, 85% hypertensive) were enrolled. Lower body negative pressure (LBNP) at -20mmHg was used to induce sympathetic activation. Rhythmic handgrip exercise at 30% of maximal voluntary contraction was performed for 3 minutes followed by 4 additional minutes with concomitant LBNP. Forearm vasoconstrictor responses were continuously monitored using near-infrared spectroscopy to detect changes in muscle tissue saturation index (TSI, calculated as % of total labile signal). A subset of CKD patients (n=49) underwent 12 weeks of aerobic cycling exercise (spinning at 85% of maximal heart rate reserve, n=29) or stretching (active control intervention, n=20)that performed 45 min/session 3d/wk and matched for duration. Results: At rest, TSI was significantly decreased in response to LBNP, with no difference between CKD and controls (dTSI: -8.0±5.9, -5.6±9.1 % respectively, p<0.05 from rest for all). During handgrip exercise, the LBNP-induced decrease in TSI was abolished with no difference between CKD and controls (dTSI: -0.9±13.2, 0.8±12.1 %; p>0.05 from rest for all). No significant changes were observed in TSI responses to LBNP during handgrip exercise after 12 weeks of cycling (dTSI: -3.6±13.8 to -3.7±12.2 %; p=0.966) or stretching (dTSI: -2.0±11.7 to -0.9±10.6 %; p=0.748) in CKD patients. Conclusion: Sympathetic vasoconstriction was blunted in the exercising forearm muscles of CKD patients, indicating intact functional sympatholysis during a small muscle upper limb exercise. Aerobic exercise training did not alter functional sympatholysis in CKD patients. Determining the exercise training prescription that has beneficial effects on autonomic regulation and exercise tolerance in CKD warrants further investigation. NIH R01HL135183; NIH R61AT10457; NIH NCATS KL2TR002381, NIH T32 DK00756; NIH F32HL147547; VA Merit I01CX001065. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.