Exercise Pressor Reflex Function Is Augmented in Rats with Chronic Kidney Disease.

Abstract

Cardiovascular responses to exercise are exaggerated in chronic kidney disease (CKD) patients. Enhanced sympathetic activation is thought to play a role with the exercise pressor reflex (EPR), a reflex originating in contracting muscle, modulating this response. Previous studies suggest an overactive EPR in CKD patients as indicated by muscle sympathetic overactivation during static handgrip exercise. However, the role of the EPR could not be fully elucidated due to experimental constraints inherent to humans. The purpose of this study was to specifically test EPR function in a CKD animal model. Male Sprague-Dawley rats were assigned to a diet containing 0.25% adenine to induce CKD or a control diet. Mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) responses to activation of the EPR, including its functional components, the mechanoreflex and metaboreflex, were assessed in decerebrate, unanesthetized animals after feeding 10 to 14 weeks. Plasma creatinine was significantly higher in CKD rats compare to controls (1.80±0.78 vs. 0.34±0.02 mg·dl^-1, P = 0.017). MAP and RSNA responses to muscle contraction (i.e., EPR activation) were potentiated in CKD rats compared to controls (Δ=36±19 vs. 17±8 mmHg, P = 0.014 and Δ=159±62 vs. 64±54 %, P = 0.004, respectively). Similarly, the pressor and sympathetic responses to passive muscle stretch (i.e., mechanoreflex stimulation) were significantly higher in CKD than in control animals. Intraarterial capsaicin administration (i.e., metaboreflex activation) induced an augmented pressor response in CKD rats, compared with controls. Our findings suggest that the EPR, stimulated by the mechano- and metaboreflex, is exaggerated in CKD.