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

Abstract

Post‐hypoxia sympathoexcitation does not elicit corresponding changes in vascular tone, suggesting diminished sympathetic signalling. Blunted sympathetic transduction following acute hypoxia, however, has not been confirmed and the effects of hypoxia on the sympathetic transduction of mean arterial pressure (MAP) as a function of action potential (AP) activity is unknown. We hypothesized that MAP changes would be blunted during acute hypoxia but restored in recovery and asynchronous APs would elicit smaller MAP changes than synchronous APs. Seven healthy males (age: 24 (3) years; BMI: 25 (3) kg/m2) underwent 20 min isocapnic hypoxia (PETO2: 47 (2) mmHg) and 30 min recovery. Multi‐unit microneurography (muscle sympathetic nerve activity; MSNA) and continuous wavelet transform with matched mother wavelet was used to detect sympathetic APs during baseline, hypoxia, early (first 7 min) and late (last 7 min) recovery. AP groups were classified as synchronous APs, asynchronous APs (occurring outside an MSNA burst) and no AP activity. Sympathetic transduction of MAP was quantified using signal‐averaging, with ΔMAP tracked following AP group cardiac cycles. Following synchronous APs, ΔMAP was reduced in hypoxia (+1.8 (0.9) mmHg) and early recovery (+1.5 (0.7) mmHg) compared with baseline (+3.1 (2.2) mmHg). AP group‐by‐condition interactions show that at rest asynchronous APs attenuate MAP reductions compared with no AP activity (−0.4 (1.1) vs. −2.2 (1.2) mmHg, respectively), with no difference between AP groups in hypoxia, early or late recovery. Sympathetic transduction of MAP is blunted in hypoxia and early recovery. At rest, asynchronous sympathetic APs contribute to neural regulation of MAP by attenuating nadir pressure responses. Key points Acute isocapnic hypoxia elicits lasting sympathoexcitation that does not correspond to parallel changes in vascular tone, suggesting blunted sympathetic transduction. Signal‐averaging techniques track the magnitude and temporal cardiovascular responses following integrated muscle sympathetic nerve activity (MSNA) burst and non‐burst cardiac cycles. However, this does not fully characterize the effects of sympathetic action potential (AP) activity on blood pressure control. We show that hypoxia blunts the sympathetic transduction of mean arterial pressure (MAP) following synchronous APs that form integrated MSNA bursts and that sympathetic transduction of MAP remains attenuated into early recovery. At rest, asynchronous APs attenuate the reduction in MAP compared with cardiac cycles following no AP activity, thus asynchronous sympathetic APs appear to contribute to the neural regulation of blood pressure. The results advance our understanding of sympathetic transduction of arterial pressure during and following exposure to acute isocapnic hypoxia in humans.

An open computational toolbox to analyze multi- and single-unit sympathetic nerve activity in microneurography

“…The software is suitable for both multi-unit and single-unit data analysis and, by employing cross-wavelet analysis and phase/latency response curves, the program quantifies dynamic changes within time, frequency, and phase domain, characterizing phase locking, transitions, and synchronizations and evaluating prominent effects on other physiological variables over subsequent and previous cyclic events in multichannel recordings. 20,37 The software testing encompassed a range of experimental conditions, including studies involving breathing stressors, such as voluntary apneas and periodic breathing, and chemoreflex challenges, such as hypoxic-normocapnic ventilatory responses (HVRs), and hypercapnic-normoxic ventilatory responses (HCVRs), thereby elucidating the dynamic aspects of sympathetic transduction to breathing disorders and chemoreflex challenges. Furthermore, the program can extend to study physiological perturbations akin to those encountered in established protocols such as the Ewing battery or other reflex assessments, i.e., baroreflex with drug challenges (phenylephrine) or ergoreflex.…”

Sympathetic transduction of cardiac sympathetic nerve activity in healthy, conscious sheep

“…A decrease in forearm conductance is also observed in cardiac cycles following a burst of MSNA, which was attenuated following the infusion of phentolamine, an α‐adrenergic blocker (Fairfax, Holwerda et al., 2013). Further studies from multiple groups have expanded on this finding to show that transduction to blood flow is dependent on the size and pattern of the MSNA bursts, that the presence of bursts can also increase arterial pressure and that this transduction can be altered both during reflex changes and in diseased states (Fairfax, Padilla, Vianna, Davis et al., 2013; Nardone et al., 2022; Shafer et al., 2023). It is important to note that these studies have not examined SNA to other vascular beds when investigating transduction to arterial pressure.…”