Role of reactive oxygen species in mediating peripheral hypoxic vasodilation and sympathoexcitation at high altitude

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. Accordingly, 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 (200mg/min for 15-min then 40mg/min) in healthy lowlanders (n=15) following 3-7 days of high altitude exposure (3800m). 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-1, p=0.007) and incidence (-5±4 bursts100HB-1, p=0.006) were both reduced. However, the infusion increased mean arterial (9±4mmHg, p≤0.001), systolic (11±8mmHg, p≤0.004), and diastolic pressure (7±4mmHg, p≤0.001), total peripheral resistance (p=0.013) concomitantly with a reduction in brachial diameter (-0.12±0.14mm, 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.