TY - JOUR
T1 - Role of reactive oxygen species in mediating peripheral hypoxic vasodilation and sympathoexcitation at high altitude
AU - Corr, Liam D.
AU - Douglas, Andrew J. M.
AU - Jenkins, Elliott J.
AU - Maier, Lauren E.
AU - Koep, Jodie L.
AU - Gibbons, Travis D.
AU - Field, Adam
AU - Anholm, James D.
AU - Foster, Katharine
AU - Adams, Zoe H.
AU - Simpson, Lydia L.
AU - Moore, Jonathan P.
AU - Traustadottir, Tinna
AU - Siebenmann, Christoph
AU - Tremblay, Joshua C.
AU - Stembridge, Mike
N1 - Publisher Copyright:
© 2025 The Author(s).
PY - 2025/12/14
Y1 - 2025/12/14
N2 - High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) via activation of the arterial chemoreflex, pulmonary arterial baroreceptors and resetting of the sympathetic vascular baroreflex. However attempting to silence these mechanisms only partially normalises MSNA, implicating other contributory mechanisms. Increased oxidant production may modulate central sympathetic outflow, while potentially modifying chemosensitivity and vasomotor signalling to the peripheral and pulmonary vasculature. Therefore we tested the hypothesis that blunting oxidative stress would reduce MSNA at high altitude. MSNA (microneurography of the peroneal nerve), continuous arterial pressure (photoplethysmography), vascular tone (duplex ultrasound of the brachial artery), pulmonary artery systolic pressure (PASP, echocardiography) and carotid body tonic activity (1-min hyperoxia) were measured pre- and post-ascorbic acid infusion (200 mg/min for 15-min and then 40 mg/min) in healthy lowlanders (n = 15) after 3–7 days of high-altitude exposure (3800 m). Ascorbic acid infusion improved the redox environment, determined by an increase in whole cell nuclear factor erythroid 2-related factor 2 activity (P = 0.005). Post-infusion MSNA burst frequency (−2 ± 2 bursts/min, P = 0.007) and incidence (−5 ± 4 bursts/100 heartbeats (HB), P = 0.006) decreased. However the infusion increased mean arterial (9 ± 4 mmHg, P≤0.001), systolic (11 ± 8 mmHg, P ≤ 0.004) and diastolic pressure (7 ± 4 mmHg, P ≤ 0.001) and total peripheral resistance (P = 0.013) concomitantly with a reduction in brachial diameter (−0.12 ± 0.14 mm, P = 0.002). Carotid body tonic activity (P = 0.247) and PASP (P = 0.365) remained unchanged by ascorbic acid infusion. In conclusion improving the antioxidant environment lowered MSNA at high altitude; however the small reduction is likely a consequence of the increased blood pressure secondary to the blunting of hypoxic vasodilation rather than a direct effect on sympathetic outflow.
[See paper for graphical abstract]
AB - High-altitude acclimatisation increases muscle sympathetic nerve activity (MSNA) via activation of the arterial chemoreflex, pulmonary arterial baroreceptors and resetting of the sympathetic vascular baroreflex. However attempting to silence these mechanisms only partially normalises MSNA, implicating other contributory mechanisms. Increased oxidant production may modulate central sympathetic outflow, while potentially modifying chemosensitivity and vasomotor signalling to the peripheral and pulmonary vasculature. Therefore we tested the hypothesis that blunting oxidative stress would reduce MSNA at high altitude. MSNA (microneurography of the peroneal nerve), continuous arterial pressure (photoplethysmography), vascular tone (duplex ultrasound of the brachial artery), pulmonary artery systolic pressure (PASP, echocardiography) and carotid body tonic activity (1-min hyperoxia) were measured pre- and post-ascorbic acid infusion (200 mg/min for 15-min and then 40 mg/min) in healthy lowlanders (n = 15) after 3–7 days of high-altitude exposure (3800 m). Ascorbic acid infusion improved the redox environment, determined by an increase in whole cell nuclear factor erythroid 2-related factor 2 activity (P = 0.005). Post-infusion MSNA burst frequency (−2 ± 2 bursts/min, P = 0.007) and incidence (−5 ± 4 bursts/100 heartbeats (HB), P = 0.006) decreased. However the infusion increased mean arterial (9 ± 4 mmHg, P≤0.001), systolic (11 ± 8 mmHg, P ≤ 0.004) and diastolic pressure (7 ± 4 mmHg, P ≤ 0.001) and total peripheral resistance (P = 0.013) concomitantly with a reduction in brachial diameter (−0.12 ± 0.14 mm, P = 0.002). Carotid body tonic activity (P = 0.247) and PASP (P = 0.365) remained unchanged by ascorbic acid infusion. In conclusion improving the antioxidant environment lowered MSNA at high altitude; however the small reduction is likely a consequence of the increased blood pressure secondary to the blunting of hypoxic vasodilation rather than a direct effect on sympathetic outflow.
[See paper for graphical abstract]
U2 - 10.1113/JP290241
DO - 10.1113/JP290241
M3 - Article (Academic Journal)
C2 - 41392360
SN - 0022-3751
JO - The Journal of Physiology
JF - The Journal of Physiology
ER -