Sympathetic overactivation explains the exaggerated exercise pressor response in chronic kidney disease

Abstract

Our previous work has shown that chronic kidney disease (CKD) patients have an exaggerated exercise blood pressure (BP) response. We hypothesized that the exaggerated BP response is mediated by overactivation of the sympathetic nervous system (SNS). We measured BP and muscle sympathetic nerve activity (MSNA) in 5 hypertensive CKD patients and 10 hypertensive controls during rhythmic handgrip (RHG 20%), and static handgrip (SHG 30%) followed by forearm posthandgrip circulatory arrest (PHGCA), during D5W infusion, and repeated in CKD patients during nitroprusside (NTP) infusion to equalize exercise‐induced BP responses. CKD patients had exaggerated increases in systolic BP during RHG 20%, SHG 30%, and PHGCA. During D5W infusion, there was no difference in MSNA responses during exercise between the groups. However, ameliorating the exaggerated BP response with NTP, and thereby eliminating baroreflex‐mediated suppression of SNS, revealed that CKD patients had significantly augmented increases in MSNA during RHG 20% and SHG 30%, but not during PHGCA. These findings suggest that the SNS overactivation is due to increased mechanoreceptor or central command activation, but not increased metaboreceptor activation. In conclusion, CKD patients have an exaggerated exercise pressor response mediated by SNS overactivation that may be due to heightened mechanoreceptor sensitivity. Supported by K grant HL098744.