Renin-Angiotensin System Blockade Is Associated with Exercise Capacity, Sympathetic Activity, and Endothelial Function in Patients with Chronic Kidney Disease

Abstract

Background: Chronic kidney disease (CKD) patients have exercise intolerance and exaggerated blood pressure reactivity during exercise that are mediated by sympathetic nervous system (SNS) overactivation and decreased nitric oxide (NO) bioavailability. The activation of the renin-angiotensin system (RAS) increases SNS activation and reduces NO synthesis, and prior studies suggest that RAS blockade attenuates declines in physical function. We hypothesized that RAS inhibitor (RASi) use is associated with higher exercise capacity mediated by decreased SNS activity and increased NO-dependent endothelial function in CKD. Method: In 35 CKD patients (57 ± 7 years) and 20 controls (CONs) (53 ± 8 years), we measured exercise capacity (peak oxygen consumption [VO_2peak]), muscle sympathetic nervous activity (MSNA), and flow-mediated dilation (FMD) for NO-dependent endothelial function. Results: CKD patients treated with RASi (CKD + RASi, n = 25) had greater VO_2peak than CKD patients not treated with RASi (CKD no RASi, n = 10), but lower VO_2peak than CONs (23.3 ± 5.8 vs. 16.4 ± 2.9, p = 0.007; vs. 30.0 ± 7.7, p = 0.016 mL/min/kg, respectively). CKD + RASi had lower resting MSNA and greater FMD than CKD no RASi. Compared to CONs, CKD + RASi had similar MSNA but lower FMD. VO_2peak was positively associated with FMD (r = 0.417, p = 0.038) and was predicted by the combination of FMD and RASi status (r² = 0.344, p = 0.01) and MSNA and RASi status (r² = 0.575, p = 0.040) in CKD patients. Conclusion: In summary, CKD patients with RASi have higher exercise capacity than those not on RASi. Higher exercise capacity in the RASi-treated group was associated with lower resting SNS activity and higher NO-dependent vascular endothelial function.