Acute intermittent hypercapnic hypoxia and sympathetic neurovascular transduction in men

Abstract

Key pointsr Intermittent hypoxia leads to long-lasting increases in muscle sympathetic nerve activity and blood pressure, contributing to increased risk for hypertension in obstructive sleep apnoea patients.r We determined whether augmented vascular responses to increasing sympathetic vasomotor outflow, termed sympathetic neurovascular transduction (sNVT), accompanied changes in blood pressure following acute intermittent hypercapnic hypoxia in men.r Lower body negative pressure was utilized to induce a range of sympathetic vasoconstrictor firing while measuring beat-by-beat blood pressure and forearm vascular conductance. r IH reduced vascular shear stress and steepened the relationship between diastolic blood pressure and sympathetic discharge frequency, suggesting greater systemic sNVT.r Our results indicate that recurring cycles of acute intermittent hypercapnic hypoxia characteristic of obstructive sleep apnoea could promote hypertension by increasing sNVT.Abstract Acute intermittent hypercapnic hypoxia (IH) induces long-lasting elevations in sympathetic vasomotor outflow and blood pressure in healthy humans. It is unknown whether IH alters sympathetic neurovascular transduction (sNVT), measured as the relationship between sympathetic vasomotor outflow and either forearm vascular conductance (FVC; regional sNVT) or diastolic blood pressure (systemic sNVT). We tested the hypothesis that IH augments sNVT by exposing healthy males to 40 consecutive 1 min breathing cycles, each comprising 40 s of hypercapnic hypoxia (P ETCO 2 : +4 ± 3 mmHg above baseline; P ETO 2 : 48 ± 3 mmHg) and 20 s of Troy J. R. Stuckless is a native of Bayside, Ontario in Canada. He attained his Bachelor of Science in Kinesiology from Queen's University and practiced as a kinesiologist in Calgary before pursuing an Master of Science from the University of British Columbia's Okanagan Campus under the supervision of Dr Glen Foster. His research interests include vascular endothelial cell function and interactions between the autonomic nervous system and cardiovascular health. Troy is currently completing the Doctor of Dental Surgery Program at the University of Toronto.normoxia (n = 9), or a 40 min air-breathing control (n = 7). Before and after the intervention, lower body negative pressure (LBNP; 3 min at -15, -30 and -45 mmHg) was applied to elicit reflex increases in muscle sympathetic nerve activity (MSNA, fibular microneurography) when clamping end-tidal gases at baseline levels. Ventilation, arterial pressure [systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP)], brachial artery blood flow (Q BA ), FVC (Q BA /MAP) and MSNA burst frequency were measured continuously. Following IH, but not control, ventilation [5 L min -1 ; 95% confidence interval (CI) = 1-9] and MAP (5 mmHg; 95% CI = 1-9) were increased, whereas FVC (-0.2 mL min -1 mmHg -1 ; 95% CI = -0.0 to -0.4) and mean shear rate (-21.9 s -1 ; 95% CI = -5.8 to -38.0; all P < 0.05) were reduced. Systemic sNVT was increased following IH (0.25 mmHg burst -1...

Peripheral chemoreflex contribution to ventilatory long‐term facilitation induced by acute intermittent hypercapnic hypoxia in males and females

“…sympathetic LTF) and often the rise in arterial blood pressure following intermittent hypoxia and in OSA (Xie et al 2000;Foster et al 2010;Gilmartin et al 2010). Additionally, our group recently observed increasedV I , arterial blood pressure and muscle sympathetic nerve activity at rest and during incremental lower body negative pressure challenges in healthy males following 40 min of IHH (Stuckless et al 2020).…”

“…However, interpretations are limited as there was not a significant increase in sympathetic vasomotor activity following the repeated apnoea protocol. Lastly, our group has recently reported augmented sympathetic neurovascular transduction following 40 min of IHH, suggesting that the elevated DBP could be due not only to an increase in sympathetic vasomotor discharge frequency but also to a greater vasoconstrictor sensitivity (Stuckless et al 2020).…”

Intermittent hypoxia and sympathetic activation: To constrict or not to constrict, that is the question

“…In the context of data reported by Stuckless et al . (2019), we speculate that IH‐mediated sympathetic vasoconstriction may occur to a greater extent in the lower vs . the upper limbs.…”

“…Unfortunately, Stuckless et al . (2019) were unable to examine lower limb blood flow and transduction as a result of the use of LBNP. For future studies, neck pressure could be considered as an alternative modality for eliciting acute increases in MSNA and would allow multisite blood flow measurements.…”

“…In agreement with the current literature, Stuckless et al . (2019) note that angiotensin‐II is an important contributor to increased sympathetic outflow and blood pressure following IH. Briefly, renal afferent chemosensory fibres detect IH‐mediated changes in perfusion and oxygenation within the kidney that elicit reflex increases in sympathetic activity and activation of the renin–angiotensin system (AlMarabeh et al .…”