Exercise pressor reflex in humans with end-stage renal disease

Abstract

Previous work has suggested that end-stage renal disease (ESRD) patients may have an exaggerated sympathetic nervous system (SNS) response during exercise. We hypothesized that ESRD patients have an exaggerated blood pressure (BP) response during moderate static handgrip exercise (SHG 30%) and that the exaggerated BP response is mediated by SNS overactivation, characterized by augmented mechanoreceptor activation and blunted metaboreceptor control, as has been described in other chronic diseases. We measured hemodynamics and muscle sympathetic nerve activity (MSNA) in 13 ESRD and 16 controls during: 1) passive hand movement (PHM; mechanoreceptor isolation); 2) low-level rhythmic handgrip exercise (RHG 20%; central command and mechanoreceptor activation); 3) SHG 30%, followed by posthandgrip circulatory arrest (PHGCA; metaboreceptor activation); and 4) cold pressor test (CPT; nonexercise stimulus). ESRD patients had exaggerated increases in systolic BP during SHG 30%; however, the absolute and relative increase in MSNA was not augmented, excluding SNS overactivation as the cause of the exaggerated BP response. Increase in MSNA was not exaggerated during RHG 20% and PHM, demonstrating that mechanoreceptor activation is not heightened in ESRD. During PHGCA, MSNA remained elevated in controls but decreased rapidly to baseline levels in ESRD, indicative of markedly blunted metaboreceptor control of MSNA. MSNA response to CPT was virtually identical in ESRD and controls, excluding a generalized sympathetic hyporeactivity in ESRD. In conclusion, ESRD patients have an exaggerated increase in SBP during SHG 30% that is not mediated by overactivation of the SNS directed to muscle. SBP responses were also exaggerated during mechanoreceptor activation and metaboreceptor activation, but without concomitant augmentation in MSNA responses. Metaboreceptor control of MSNA was blunted in ESRD, but the overall ability to mount a SNS response was not impaired. Other mechanisms besides SNS overactivation, such as impaired vasodilatation, should be explored to explain the exaggerated exercise pressor reflex in ESRD.

Fig. 1.

Timeline of experimental protocol. After a satisfactory nerve recording was obtained, 10 min of rest were given, followed by a baseline recording of muscle sympathetic nerve activity (MSNA) for 10 min. Heart rate, blood pressure, and MSNA were recorded throughout the protocol. After the baseline recording, the participant underwent 4 maneuvers in random order: 1) rhythmic handgrip exercise (RHG 20%) at 20% maximum voluntary contraction (MVC) for 3 min; 2) static handgrip exercise at 30% MVC (SHG 30%) for 3 min followed by posthandgrip circulatory arrest (PHGCA) for 2 min; 3) passive hand movement (PHM) for 3 min; and 4) cold pressor test (CPT) for 1 min. CPT was performed in a subset of participants. Rest (40 min) was allowed between each maneuver to allow MSNA, blood pressure, and heart rate to return to baseline levels before initiation of the next maneuver.

Fig. 2.

Hemodynamic changes during experimental maneuvers. The %change from resting baseline levels in systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) depicted during each experimental maneuver in control participants (black bars) and end-stage renal disease (ESRD) patients (gray bars). %ΔBP, % change from baseline in mm Hg for SBP and DBP; %ΔHR, % change from baseline in heart rate in beats per minute (bpm). Values are expressed as means ± SE. *P < 0.05.

Fig. 3.

Percent change in MSNA during SHG followed by PHGCA. Percent change from resting baseline in MSNA during each minute (M) of SHG followed by PHGCA in controls (closed circles) vs. ESRD patients (open circles). A: %change from baseline in MSNA burst frequency quantitated as bursts/min. B: %change in MSNA quantitated as total activity in units/min. Values are expressed as means ± SE. The overall ANOVA F-test was significant for a difference between the two groups (see results). *P < 0.05 for a difference between the two groups at that time point.

Fig. 4.

Percent Change in MSNA during PHM. Percent change from baseline in MSNA during each minute of PHM. A: %change in MSNA quantitated as bursts/min. B: %percent change in MSNA quantitated as total activity in units/min. Values are expressed as means ± SE. The overall ANOVA F-test was nonsignificant (NS) (see results).

Fig. 5.

Percent change in MSNA during rhythmic handgrip. Percent change in MSNA during each minute of RHG at 20% MVC (RHG 20%). A: %change in MSNA quantitated as bursts/min. B: %change in MSNA quantitated as total activity in units/min. Values are expressed as means ± SE. The overall ANOVA F-test was nonsignificant (see results).

Fig. 6.

Percent change in MSNA during PHGCA and CPT. Percent change from resting baseline MSNA. ESRD indicates end-stage renal disease. *P < 0.05.