Muscle Metaboreflex Control of Sympathetic Activity Is Preserved after Acute Intermittent Hypercapnic Hypoxia

Abstract

PurposeIn normotensive patients with obstructive sleep apnea (OSA), the muscle sympathetic nerve activity (MSNA) response to exercise is increased while metaboreflex control of MSNA is decreased. We tested the hypotheses that acute intermittent hypercapnic hypoxia (IHH) in males free from OSA and associated comorbidities would augment the MSNA response to exercise but attenuate the change in MSNA during metaboreflex activation.MethodsThirteen healthy males (age = 24 ± 4 yr) were exposed to 40 min of IHH. Before and after IHH, the pressor response to exercise was studied during 2 min of isometric handgrip exercise (at 30% maximal voluntary contraction), whereas the metaboreflex was studied during 4 min of postexercise circulatory occlusion (PECO). Mean arterial pressure (MAP), heart rate (HR), and fibular MSNA were recorded continuously. MSNA was quantified as burst frequency (BF) and total activity (TA). Mixed effects linear models were used to compare the exercise pressor and metaboreflex before and after IHH.ResultsAs expected, IHH led to significant increases in MSNA BF, TA, and MAP at baseline and throughout exercise and PECO. However, during handgrip exercise, the change from baseline in MAP, HR, MSNA BF, and TA was similar before and after IHH (All P > 0.31). During PECO, the change from baseline in MSNA BF and TA was similar after IHH, whereas the change from baseline in MAP (Δ14 mm Hg, 95% CI = 7–19, vs Δ16 mm Hg, 95% CI = 10–21; P < 0.01) was modestly increased.ConclusionAfter acute IHH, MSNA response to handgrip exercise and metaboreflex activation were preserved in healthy young males despite overall increases in resting MSNA and MAP. Chronic IHH and comorbidities often associated with OSA may be required to modulate the exercise pressor reflex and metaboreflex.

Action potential amplitude and baroreflex resetting of action potential clusters mediate hypoxia‐induced sympathetic long‐term facilitation

“…Homeostatic disturbances in oxygen tension are detected by peripheral chemoreceptors, which initiate a reflexive increase in sympathetic outflow and arterial pressure (Prabhakar et al, 2015). In healthy individuals, exposure to acute bouts of hypoxia produces long-lasting sympathetic activation and augmented blood pressures (Foster et al, 2010;Jouett et al, 2017;Ott et al, 2020;Querido et al, 2010Querido et al, , 2011Shafer et al, 2021;Stuckless et al, 2020;Vermeulen et al, 2020;Xie et al, 2001). Sympathetic long-term facilitation (sLTF) elicited by acute isocapnic hypoxia (Xie et al, 2001) is facilitated by an upward resetting of the sympathetic arterial baroreflex, which remains reset for at least 20 min (Querido et al, 2011).…”

The coronary vascular response to the metaboreflex at low altitude and during acute and prolonged high altitude in males

“…This duration of PECO was required to provide sufficient time for echocardiography image acquisition. Our previous work, illustrates good stability in cardiovascular and sympathetic parameters across a similar duration of PECO (19,31). During the handgrip exercise, handgrip intensities were displayed on a screen in real-time and a guideline was set to 30 % MVC so participants had visual feedback to gauge their intensity.…”

Acute hypoxia elicits lasting reductions in the sympathetic action potential transduction of arterial blood pressure in males

“…Females were excluded from participation, as data collection was conducted during a fixed 3-week time frame in collaboration with microneurographers visiting our laboratory. In that time, two distinct experimental protocols were performed investigating neural sympathetic response to blood gas alterations and in response to exercise (Incognito et al, 2021;Shafer et al, 2021Shafer et al, , 2022. Due to sex-based differences in basal MSNA (Joyner et al, 2015) and neurovascular regulation (Briant et al, 2016), it was not possible to effectively control for the menstrual cycle phase or meet the sample size requirements needed to account for sex-based differences during this window of experimentation.…”

“…Hypoxia-induced chemoreflex activation elicits an increase in sympathetic outflow to the skeletal muscle vasculature, which remains elevated even when blood gases return to normal (Foster et al, 2010;Jouett et al, 2017;Ott et al, 2020;Querido et al, 2010Querido et al, , 2011Shafer et al, 2021Shafer et al, , 2022Steele, Skow et al, 2021;Stuckless et al, 2020;Vermeulen et al, 2020;Xie et al, 2001). Sympathoexcitation during and following hypoxia appears to be mediated by a resetting of the baroreflex to higher operating points (Cooper et al, 2005;Halliwill et al, 2003;Querido et al, 2011;Shafer et al, 2022;Tremblay et al, 2016).…”