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...

Ventilatory long-term facilitation (vLTF) refers to respiratory neuroplasticity that develops following intermittent hypoxia in both healthy and clinical populations. r A sustained hypercapnic background is argued to be required for full vLTF expression in humans. r We determined whether acute intermittent hypercapnic hypoxia elicits vLTF during isocapnic-normoxic recovery in healthy males and females. We further assessed whether tonic peripheral chemoreflex drive is necessary and contributes to the expression of vLTF. r Following 40 min of intermittent hypercapnic hypoxia, minute ventilation was increased throughout 50 min of isocapnic-normoxic recovery. Inhibition of peripheral chemoreflex drive with hyperoxia attenuated the magnitude of vLTF. r Males and females achieve vLTF through different respiratory recruitment patterns.

Key points We investigated the influence of arterial PnormalCO2 (PnormalaCO2) with and without acutely elevated arterial pH and bicarbonate ([HCO3–]) on cerebral blood flow (CBF) regulation in the internal carotid artery and vertebral artery. We assessed stepwise iso‐oxic alterations in PnormalaCO2 (i.e. cerebrovascular CO2 reactivity) prior to and following i.v. sodium bicarbonate infusion (NaHCO3–) to acutely elevate arterial pH and [HCO3–]. Total CBF was unchanged irrespective of a higher arterial pH at each matched stage of PnormalaCO2, indicating that CBF is acutely regulated by PnormalaCO2 rather than arterial pH. The cerebrovascular responses to changes in arterial H+/pH were altered in keeping with the altered relationship between PnormalaCO2 and H+/pH following NaHCO3– infusion (i.e. changes in buffering capacity). Total CBF was ∼7% higher following NaHCO3– infusion during isocapnic breathing providing initial evidence for a direct vasodilatory influence of HCO3– independent of PnormalaCO2 levels. Abstract Cerebral blood flow (CBF) regulation is dependent on the integrative relationship between arterial PnormalCO2 (PnormalaCO2), pH and cerebrovascular tone; however, pre‐clinical studies indicate that intrinsic sensitivity to pH, independent of changes in PnormalaCO2 or intravascular bicarbonate ([HCO3–]), principally influences cerebrovascular tone. Eleven healthy males completed a standardized cerebrovascular CO2 reactivity (CVR) test utilizing radial artery catheterization and Duplex ultrasound (CBF); consisting of matched stepwise iso‐oxic alterations in PnormalaCO2 (hypocapnia: –5, –10 mmHg; hypercapnia: +5, +10 mmHg) prior to and following i.v. sodium bicarbonate (NaHCO3–; 8.4%, 50 mEq 50 mL–1) to elevate pH (7.408 ± 0.020 vs. 7.461 ± 0.030; P < 0.001) and [HCO3–] (26.1 ± 1.4 vs. 29.3 ± 0.9 mEq L–1; P < 0.001). Absolute CBF was not different at each stage of CO2 reactivity (P = 0.629) following NaHCO3–, irrespective of a higher pH (P < 0.001) at each matched stage of PnormalaCO2 (P = 0.927). Neither hypocapnic (3.44 ± 0.92 vs. 3.44 ± 1.05% per mmHg PnormalaCO2; P = 0.499), nor hypercapnic (7.45 ± 1.85 vs. 6.37 ± 2.23% per mmHg PnormalaCO2; P = 0.151) reactivity to PnormalaCO2 were altered pre‐ to post‐NaHCO3–. When indexed against arterial [H+], the relative hypocapnic CVR was higher (P = 0.019) and hypercapnic CVR was lower (P = 0.025) following NaHCO3–, respectively. These changes in reactivity to [H+] were, however, explained by alterations in buffering between PnormalaCO2 and arterial H+/pH consequent to NaHCO3–. Lastly, CBF was higher (688 ± 105 vs. 732 ± 89 mL min–1, 7% ± 12%; P = 0.047) following NaHCO3– during isocapnic breathing providing support for a direct influence of HCO3– on cerebrovascular tone independent of PnormalaCO2. These data indicate that in the setting of acute metabolic alkalosis, CBF is regulated by PnormalaCO2 rather than arterial pH.

Reducing the work of breathing during exercise improves locomotor muscle blood flow and reduces diaphragm and locomotor muscle fatigue and is thought to be the result of a sympathetically mediated reflex. Aim: The aim of this study was to assess muscle sympathetic nerve activity (MSNA) when the work of breathing is experimentally lowered during dynamic exercise. Methods: Healthy subjects (n = 12; age = 29 ± 9 years) performed semi-recumbent cycling trials at 40%, 60%, and 80% of peak workload. Exercise trials consisted of spontaneous breathing, reduced work of breathing (proportional assist ventilator), followed by further spontaneous breathing (post-ventilator). MSNA was recorded from the median nerve. Results: There was no difference in work of breathing between PAV and post-PAV at 40% peak work. At 60% peak work, the ventilator significantly (P < 0.05) reduced work of breathing (103 ± 39 vs 144 ± 47 J min −1 ), sympathetic nerve activity (35 ± 5 vs 42 ± 8 burst min −1 ), and _ VO 2 (2.4 ± 0.5 vs 2.6 ± 0.5 L min −1 ) without influencing ventilation (86 ± 9 vs 82 ± 10 L min −1 ; P > 0.05), for PAV and post-PAV respectively. During 80% peak work (n = 8), the ventilator significantly (P < 0.05) reduced work of breathing (235 ± 110 vs. 361 ± 150 J min −1 ), MSNA (48 ± 7 vs 54 ± 11 burst min −1 ), and _ VO 2 (2.9 ± 0.6 vs 3.2 ± 0.7 L min −1 ) but not ventilation (121 ± 20 vs 123 ± 20 L min −1 ; P > 0.05), for PAV and post-PAV respectively. There was a significant relationship between MSNA and _ VO 2 (P < 0.0001) with a significant interaction due to the ventilator (P < 0.05). Conclusion: Lowering the normally occurring work of breathing during exercise results in commensurate reductions in MSNA. Our findings provide evidence of a sympathetically mediated vasoconstrictor effect emanating from respiratory muscles during exercise. K E Y W O R D S blood flow distribution, exercise physiology, proportional assist ventilation, respiratory metaboreflex Paolo B. Dominelli and Keisho Katayama contributed equally to this work.