Dissecting the exercise pressor reflex in heart failure: A multi-step failure

Figures

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  Fig. 1.. Schematic representation of the exercise pressor reflex (EPR). The left and the right segments of the schematic depict the afferent and efferent arms of the EPR, respectively. Other sympatho-excitatory (i.e., central command and chemoreceptors) and sympatho-inhibitory (baroreceptors) signals are also represented. Numbers denote known sites of EPR-related signaling alterations in heart failure (HF). (1) Mechanical and metabolic perturbations during exercise are sensed by the group III/IV muscle afferents. Resulting from disease-related skeletal muscle abnormalities, exercise-induced metabolic perturbation in the muscle interstitium is, at any given workload, larger in patients with HF compared to healthy controls. (2) However, the exacerbated metabolic milieu in HF may not necessarily result in overactivation of the metabosensitive afferents and, thus, the EPR. In fact, the sensitivity of group IV muscle afferents has been found to be unchanged or even blunted, and hyper-sensitive group III neurons might largely account for the excessive EPR in HF. (3) The dorsal horn is the first level of group III/IV muscle afferent feedback processing within the spinal cord and represents a…

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  Fig. 2.. Discharge frequency of group III and IV afferents in response to static contraction induced by electrical stimulation of L5 ventral root, to passive stretch and to capsaicin in sham and rats with heart failure (CHF). Mean data illustrating (A) the baseline discharge of group III and IV muscle afferents in sham and HF rats, and (B) the responses of these sensory neurons to static contraction induced by electrical stimulation of L5 ventral root. Panel C and D illustrate mean data showing the response of group III and IV muscle afferents to (C) two levels of passive stretch and (D) two doses of capsaicin in sham and CHF rats. Data are expressed as mean ± SEM. *P < 0.05 vs. sham, †P < 0.05 vs. lower level of stretch or lower dose of capsaicin. From Wang et al.(Wang et al., 2010).

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  Fig. 3.. Impact of HF on afferent signal transmission within the dorsal horn of the spinal cord. Panel (A): microdialysis data reflecting increased glutamate release during a 4-min intermittent static contraction (30-s on, 30-s off) in congestive heart failure (CHF) rats compared with sham-operated (sham) rats. Data are expressed as mean ± SEM. * P < 0.05 vs. baseline; # P < 0.05 vs. sham rats. Panel (B): effects of microinjection of glutamate (10 mM, 100 nl) into the L4 or L5 dorsal horn on mean arterial pressure (MAP) in sham and CHF rats. ABP, arterial blood pressure. Data are expressed as mean ± SE; n = 6 rats/group. *P < 0.05 vs. sham rats. Adapted from Wang et al.(Wang et al., 2015).

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  Fig. 4.. Effect of microinjection of bicuculline into the PVN on (A) renal nerve discharge and (B) mean arterial blood pressure in sham-operated control and heart failure rats. Values represent means ± SE; * P < 0.05 vs. sham. Adapted from Zhang et al.(Zhang et al., 2002).

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  Fig. 5.. Phenylephrine-induced changes (%) in leg blood flow (A) and leg vascular conductance (B) at rest, and the magnitude of sympatholysis during single leg knee extension exercise (C) in control participants and in heart failure patients with preserved ejection fraction (HFpEF). * P < 0.05 vs. control; # P < 0.05 vs. pre-infusion. ‡P < 0.05 vs. 0 W. Adapted from Alpenglow et al. (Alpenglow et al., 2024).