Peer reviewed version Cyswllt i'r cyhoeddiad / Link to publication Dyfyniad o'r fersiwn a gyhoeddwyd / Citation for published version (APA): Abstract 47 Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to 48 high-altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated 49 dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular 50 constraint, or consequential altered

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... (e.g. shear stress) associated with increased 51 SNA as a consequence of exposure to HA. We hypothesized that: 1) at rest, SNA would be 52 elevated and FMD would be reduced at HA compared to sea-level (SL); and 2) at SL and HA, 53 FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely 54 decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at 55 SL (344m) and HA (5050m) in 14 participants during mild lower-body negative pressure 56 (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure 57 (finger photoplethysmography), heart rate (electrodcardiogram), oxygen saturation (pulse 58 oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded 59 during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a 60 subset of participants (n=5). Our findings were: 1) at rest, SNA was elevated (P<0.01), and 61 absolute FMD was reduced (P=0.024), but relative FMD remained unaltered (P=0.061), at HA 62 compared to SL, and 2) despite significantly altering SNA with LBNP (+60.3±25.5%) and LBPP 63 (-37.2±12.7%) (P<0.01), FMD was unaltered at SL (P=0.448), and HA (P=0.537). These data 64 indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL 65 or HA. 66 67 New and Noteworthy: The role of the sympathetic nervous system on endothelial function 68 remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic 69 nervous activity at sea-level and high-altitude, and measured brachial endothelial function via 70 flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no 71 effect on endothelial function. 72 73 74 by 10.220.33.2 on September 20, 2017 http://jap.physiology.org/ Downloaded from Abbreviations: 75 CO, cardiac output 76 FMD, flow-mediated dilatation 77 HR, heart rate 78 LBNP, lower-body negative pressure 79 LBPP, lower-body positive pressure 80 MAP, mean arterial pressure 81 MSNA, muscle sympathetic nervous activity 82 SNA, sympathetic nervous activity 83 SpO 2 , peripheral oxyhemoglobin saturation 84 SRAUC, shear rate area under the curve 85 SV, stroke volume 86 TPR, total peripheral resistance 87 88 89 Downloaded from 129 hypoxia when resting SNA is markedly elevated (15, 23). 130 By employing a counter-balanced, randomized design, the primary purposes of the 131 current study were to investigate the role of the sympathetic nervous activity on endothelial 132 function at sea-level (344m), and during chronic exposure to hypobaric hypoxia (5050m) where 133 resting sympathetic nervous activity is chronically elevated (15, 23). By using a novel, purpose 134 built, light-weight, portable lower-body differential pressure chamber to alter sympathetic 135 nervous activity largely independent of hemodynamics, we hypothesized that: 1) at rest, 136 by 10.220.33.2 on September 20, 2017 http://jap.physiology.org/ Downloaded from sympathetic nervous activity would be elevated, and endothelial function would be reduced at 137 high-altitude compared to sea-level, 2) at sea-level and after acclimatization to high-altitude, 138 endothelial function would be reduced during an acute increase in sympathetic nervous activity 139 (induced by mild lower-body negative pressure), and elevated during an acute decrease in 140 sympathetic nervous activity (induced by mild lower-body positive pressure), independent of 141 changes in peripheral hemodynamics.