Exercise pressor response and arterial baroreflex unloading during exercise in chronic kidney disease

Abstract

Patients with chronic kidney disease (CKD) have poor exercise capacity, which contributes to cardiovascular risk. We sought to determine whether patients with stage 2 or stage 3 CKD have an augmented blood pressure (BP) response during exercise, and if so, whether overactivation of the sympathetic nervous system (SNS) during exercise might play a role. In 13 patients with CKD and hypertension and 13 controls with hypertension, we measured hemodynamics and muscle sympathetic nerve activity (MSNA) during the following maneuvers: low-level rhythmic handgrip (RHG 20%), which primarily stimulates mechanoreceptors, and moderate static handgrip exercise (SHG 30%) followed by posthandgrip circulatory arrest (PHGCA), which isolates metaboreceptors. During baseline studies, patients with CKD had significantly greater increases in mean arterial pressure (MAP) during SHG 30% (P = 0.045), RHG 20% (P = 0.031), and PHGCA (P = 0.043); however, the MSNA response was not augmented in patients with CKD compared with controls. We hypothesized that an augmented SNS response during exercise might be revealed in CKD if arterial baroreflex constraint was equalized using nitroprusside (NTP). These exercise maneuvers were repeated in patients with CKD during NTP infusion to equalize the BP response between groups, thereby relieving baroreflex-mediated suppression of SNS activity. With NTP infusion, patients with CKD had significantly increased MSNA responses during SHG 30% (P = 0.0044), and RHG 20% (P = 0.0064), but not during PHGCA (P > 0.05), suggesting increased reflex activation of the SNS during exercise, which may be mediated by mechanoreceptors but not metaboreceptors. Patients with CKD have an exaggerated BP response during rhythmic and static exercise with underlying SNS overactivation that is revealed during arterial baroreflex unloading during exercise.

Fig. 1.

Hemodynamic changes during static handgrip exercise. Percent (%) change and absolute (Δ) change from baseline (BL) levels in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) during each minute (M) of static handgrip exercise (SHG 30%) in controls during D5W infusion (CON+D5W, open circles), patients with chronic kidney disease (CKD) during D5W infusion (CKD+D5W, filled circles), and patients with CKD during nitroprusside infusion (CKD+NTP, filled circles with dotted lines). Values are expressed as means ± SE. †Indicates overall ANOVA F-test was significant for a difference between CON+D5W vs. CKD+D5W groups (see RESULTS). *Indicates P < 0.05 in the difference between CON+D5W vs. CKD+D5W groups at that time point.

Fig. 2.

Change in MSNA during SHG 30%, RHG 20%, and PHGCA. Change from baseline (BL) in muscle sympathetic nerve activity (MSNA) during each minute (M) of rhythmic (RHG 20%) handgrip exercise, static (SHG 30%) handgrip exercise, and posthandgrip circulatory arrest (PHGCA) in controls during D5W infusion (CON+D5W, open circles), patients with chronic kidney disease (CKD) during D5W infusion (CKD+D5W, filled circles), and patients with CKD during nitroprusside infusion (CKD+NTP, filled circles with dotted lines). MSNA was quantified as bursts/minute and total activity (units/min). Relative (%) change in MSNA, and absolute (Δ) change in MSNA were quantified for both total activity and burst frequency in bursts/minute. Values are expressed as means ± SE. †Indicates ANOVA F-test was significant for a difference between CON+D5W vs. CKD+D5W groups (see RESULTS). *Indicates P < 0.05 in the difference between CON+D5W vs. CKD+D5W groups at that time point. **Indicates P < 0.05 in the difference between CON+D5W vs. CKD+NTP groups at that time point. ‡Indicates ANOVA F-test was significant for a difference between CON+D5W vs. CKD+NTP. In I–L, P values are shown for CON+D5W vs. (VS) both CKD+D5W and CKD+NTP.

Fig. 3.

Absolute levels of MSNA during static and rhythmic handgrip exercise. Absolute levels of muscle sympathetic nerve activity (MSNA) quantified as bursts/minute at baseline (BL) and during each minute (M) of static (SHG 30%) and rhythmic (RHG 20%) handgrip exercise. The overall ANOVA F-test was significant for a difference between controls during D5W infusion (CON+D5W) compared with patients with chronic kidney disease (CKD) during nitroprusside infusion (CKD+NTP) (see RESULTS). *P < 0.05 in the difference between the two groups at that time point.

Fig. 4.

Hemodynamic changes during rhythmic handgrip exercise. Percent (%) change and absolute (Δ) change from baseline (BL) levels in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) during each minute (M) of rhythmic handgrip exercise (RHG 20%) in controls during D5W infusion (CON+D5W, open circles), patients with chronic kidney disease (CKD) during D5W infusion (CKD+D5W, filled circles), and patients with CKD during nitroprusside infusion (CKD+NTP, filled circles with dotted lines). Values are expressed as means ± SE. *Indicates P < 0.05 in the difference between CON+D5W vs. CKD+D5W groups at that time point. †Indicates overall ANOVA F-test was significant for a difference between CON+D5W vs. CKD+D5W groups (see RESULTS).

Fig. 5.

Hemodynamic changes during posthandgrip circulatory arrest. Percent (%) change and absolute (Δ) change from baseline (BL) levels in systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) during each minute (M) of posthandgrip circulatory arrest (PHGCA) in controls during D5W infusion (CON+D5W, open circles), patients with chronic kidney disease (CKD) during D5W infusion (CKD+D5W, filled circles), and patients with CKD during nitroprusside infusion (CKD+NTP, filled circles with dotted lines). Values are expressed as means ± SE. *Indicates P < 0.05 in the difference between CON+D5W vs. CKD+D5W groups at that time point. **Indicates P < 0.05 in the difference between the CON+D5W vs. CKD+NTP groups at that time point. †Indicates ANOVA F-test was significant in the difference between CON+D5W vs. CKD+D5W groups (see RESULTS). ‡Indicates ANOVA F-test was significant in the difference between CON+D5W vs. CKD+NTP.