Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men

Abstract

Edgell H, Stickland MK. Activation of the carotid chemoreflex secondary to muscle metaboreflex stimulation in men. Am J Physiol Regul Integr Comp Physiol 306: R693-R700, 2014. First published February 26, 2014 doi:10.1152 doi:10. /ajpregu.00472.2013 has shown that the carotid chemoreceptor (CC) contributes to sympathetic control of cardiovascular function during exercise, despite no evidence of increased circulating CC stimuli, suggesting enhanced CC activity/sensitivity. As interactions between metaboreceptors and chemoreceptors have been previously observed, the purpose of this study was to isolate the metaboreflex while acutely stimulating or inhibiting the CC to determine whether the metaboreflex increased CC activity/sensitivity. Fourteen young healthy men (height: 177.0 Ϯ 2.1 cm, weight: 85.8 Ϯ 5.5 kg, age: 24.6 Ϯ 1.1 yr) performed three trials of 40% maximal voluntary contraction handgrip for 2 min, followed by 3 min of postexercise circulatory occlusion (PECO) to stimulate the metaboreflex. In random order, subjects either breathed room air, hypoxia (target SPO 2 ϭ 85%), or hyperoxia (FIO 2 ϭ 1.0) during the PECO to modulate the chemoreflex. After these trials, a resting hypoxia trial was conducted without handgrip or PECO. Ventilation (V E), heart rate (HR), blood pressure, and muscle sympathetic nervous activity (MSNA) data were continuously obtained. Relative to normoxic PECO, inhibition of the CC during hyperoxic PECO resulted in lower MSNA (P ϭ 0.038) and HR (P ϭ 0.021). Relative to normoxic PECO, stimulation of the CC during hypoxic PECO resulted in higher HR (P Ͻ 0.001) and V E (P Ͻ 0.001). The ventilatory and MSNA responses to hypoxic PECO were not greater than the sum of the responses to hypoxia and PECO individually, indicating that the CC are not sensitized during metaboreflex activation. These results demonstrate that stimulation of the metaboreflex activates, but does not sensitize the CC, and help explain the enhanced CC activity with exercise. sympathetic nerve activity; ventilation; exercise EXERCISE is known to involve cardiovascular influences from metaboreceptors, mechanoreceptors, baroreceptors, and central command (25). The carotid chemoreceptor has been shown to be activated/sensitized during exercise (10,27,33,40). Previous work has provided evidence that the carotid chemoreceptor is enhanced with exercise despite no change in circulating carotid chemoreceptor stimuli (K ϩ , lactate, pH, PCO 2 , PO 2 ), and that carotid chemoreceptor inhibition with either dopamine or hyperoxia increases cardiac output and/or peripheral blood flow during exercise secondary to a reduction in sympathetic vasoconstrictor outflow (32-34). Similarly, rhythmic handgrip exercise in humans activates/sensitizes the carotid chemoreceptor despite no increase in blood lactate (34); however, the exact mechanism behind this activation/sensitization of the carotid chemoreceptor during exercise is unknown.Conflicting evidence exists concerning the role of muscle afferents on exercise-induced carotid chemorecepto...

Sex differences in the ventilatory and cardiovascular response to supine and tilted metaboreflex activation

“…Edgell and Stickland () observed that the peripheral chemoreflex was activated secondary to metaboreflex activation in men supporting our findings of elevated ventilation in men during PECO (which has been observed previously in all male groups or groups including mostly men (Braz et al. ; Houssiere et al.…”

“…; Edgell and Stickland ). During PECO (i.e., metaboreflex activation due to metabolite accumulation), men have reduced MCA conductance with a concurrent decrease in end‐tidal CO 2 (potentially due to hyperventilation from interactions with the chemoreflex (Edgell and Stickland ; Patrick and Caterisano ; Saito et al. ) or perhaps via a direct influence on control centres in the medulla such as the nucleus tractus solitarius (Sander et al.…”

Sensitivity of the human ventilatory response to muscle metaboreflex activation during concurrent mild hypercapnia

“…systemic normocapnia) did abolish the ventilatory response during PECO, supporting a major role for central chemoreception in helping to generate the response (Bruce & White, ). Edgell and Stickland () report that hypoxic activation of the carotid chemoreflex combined with PECO does increase ventilation but that this increase is not greater than the sum of responses to hypoxia and PECO individually. They argue that this indicates that the metaboreflex does not sensitize the carotid chemoreflex.…”

Carotid chemoreflex and muscle metaboreflex interact to the regulation of ventilation in patients with heart failure with reduced ejection fraction

“…Some studies in healthy young adults have employed hypoxia during concomitant activation of skeletal muscle afferents. For instance, simultaneous carotid chemoreceptors activation via hypoxia and muscle metaboreflex activation via posthandgrip ischemia tended ( p = .14) to provoke greater response than the sum of responses to each separated stimulus in healthy young men, in spite of P ET CO 2 being ~7 mmHg lower during hypoxic posthandgrip ischemia versus normoxic posthandgrip ischemia (Edgell & Stickland, ). Consequently, the difference between experimental and calculated sums could have been clearer at comparable P ET CO 2 level.…”

“…In contrast, however, the carotid chemoreflex does not seem to contribute to and respiratory pattern regulation during recovery from exercise in humans (Clement et al, ; Paula‐Ribeiro et al, ). Thus, an interaction among the carotid chemoreflex and other reflexes that operate during exercise, but not during recovery, possibly exist (Edgell & Stickland, ; Gujic et al, ; Scott et al, ).…”