TY - JOUR

T1 - Baroreflex Control of Sympathetic Vasomotor Activity and Resting Arterial Pressure at High Altitude: Insight from Lowlanders and Sherpa

AU - Simpson, Lydia

AU - Busch, Steven

AU - Oliver, Samuel

AU - Ainslie, Phil

AU - Stembridge, Mike

AU - Steinback, Craig

AU - Moore, Jonathan

N1 - Funding Information Natural Sciences and Engineering Research Council of Canada. Grant Numbers: RGPIN‐2014‐06637, RGPIN‐2015‐0821‐01 Canada Research Chairs. Grant Number: 950‐2309970 University of Alberta. Grant Number: HPF162 © 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - KEY POINTS: Hypoxia, a potent activator of the sympathetic nervous system, is known to increase muscle sympathetic nerve activity (MSNA) to the peripheral vasculature of native Lowlanders during sustained high altitude (HA) exposure. We show that the arterial baroreflex control of MSNA functions normally in healthy Lowlanders at HA, and that upward baroreflex resetting permits chronic activation of basal sympathetic vasomotor activity under this condition. The baroreflex MSNA operating point and resting sympathetic vasomotor outflow both are lower for highland Sherpa compared to acclimatizing Lowlanders; these lower levels may represent beneficial hypoxic adaptation in Sherpa. Acute hyperoxia at HA had minimal effect on baroreflex control of MSNA in Lowlanders and Sherpa, raising the possibility that mechanisms other than peripheral chemoreflex activation contribute to vascular sympathetic baroreflex resetting and sympathoexcitation. These findings provide a better understanding of sympathetic nervous system activation and the control of blood pressure during the physiological stress of sustained HA hypoxia.ABSTRACT: Exposure to high altitude (HA) is characterized by heightened muscle sympathetic neural activity (MSNA); however, the effect on arterial baroreflex control of MSNA is unknown. Furthermore, arterial baroreflex control at HA may be influenced by genotypic and phenotypic differences between lowland and highland natives. Fourteen Lowlanders (12 male) and nine male Sherpa underwent haemodynamic and sympathetic neural assessment at low altitude (Lowlanders, low altitude; 344 m, Sherpa, Kathmandu; 1400 m) and following gradual ascent to 5050 m. Beat-by-beat haemodynamics (photoplethysmography) and MSNA (microneurography) were recorded lying supine. Indices of vascular sympathetic baroreflex function were determined from the relationship of diastolic blood pressure (DBP) and corresponding MSNA at rest (i.e. DBP 'operating pressure' and MSNA 'operating point'), as well as during a modified Oxford baroreflex test (i.e. 'gain'). Operating pressure and gain were unchanged for Lowlanders during HA exposure; however, the operating point was reset upwards (48 ± 16 vs. 22 ± 12 bursts 100 HB -1 , P = 0.001). Compared to Lowlanders at 5050 m, Sherpa had similar gain and operating pressure, although the operating point was lower (30 ± 13 bursts 100 HB -1 , P = 0.02); MSNA burst frequency was lower for Sherpa (22 ± 11 vs. 30 ± 9 bursts min -1 P = 0.03). Breathing 100% oxygen did not alter vascular sympathetic baroreflex function for either group at HA. For Lowlanders, upward baroreflex resetting promotes heightened sympathetic vasoconstrictor activity and maintains blood pressure stability, at least during early HA exposure; mechanisms other than peripheral chemoreflex activation could be involved. Sherpa adaptation appears to favour a lower sympathetic vasoconstrictor activity compared to Lowlanders for blood pressure homeostasis.

AB - KEY POINTS: Hypoxia, a potent activator of the sympathetic nervous system, is known to increase muscle sympathetic nerve activity (MSNA) to the peripheral vasculature of native Lowlanders during sustained high altitude (HA) exposure. We show that the arterial baroreflex control of MSNA functions normally in healthy Lowlanders at HA, and that upward baroreflex resetting permits chronic activation of basal sympathetic vasomotor activity under this condition. The baroreflex MSNA operating point and resting sympathetic vasomotor outflow both are lower for highland Sherpa compared to acclimatizing Lowlanders; these lower levels may represent beneficial hypoxic adaptation in Sherpa. Acute hyperoxia at HA had minimal effect on baroreflex control of MSNA in Lowlanders and Sherpa, raising the possibility that mechanisms other than peripheral chemoreflex activation contribute to vascular sympathetic baroreflex resetting and sympathoexcitation. These findings provide a better understanding of sympathetic nervous system activation and the control of blood pressure during the physiological stress of sustained HA hypoxia.ABSTRACT: Exposure to high altitude (HA) is characterized by heightened muscle sympathetic neural activity (MSNA); however, the effect on arterial baroreflex control of MSNA is unknown. Furthermore, arterial baroreflex control at HA may be influenced by genotypic and phenotypic differences between lowland and highland natives. Fourteen Lowlanders (12 male) and nine male Sherpa underwent haemodynamic and sympathetic neural assessment at low altitude (Lowlanders, low altitude; 344 m, Sherpa, Kathmandu; 1400 m) and following gradual ascent to 5050 m. Beat-by-beat haemodynamics (photoplethysmography) and MSNA (microneurography) were recorded lying supine. Indices of vascular sympathetic baroreflex function were determined from the relationship of diastolic blood pressure (DBP) and corresponding MSNA at rest (i.e. DBP 'operating pressure' and MSNA 'operating point'), as well as during a modified Oxford baroreflex test (i.e. 'gain'). Operating pressure and gain were unchanged for Lowlanders during HA exposure; however, the operating point was reset upwards (48 ± 16 vs. 22 ± 12 bursts 100 HB -1 , P = 0.001). Compared to Lowlanders at 5050 m, Sherpa had similar gain and operating pressure, although the operating point was lower (30 ± 13 bursts 100 HB -1 , P = 0.02); MSNA burst frequency was lower for Sherpa (22 ± 11 vs. 30 ± 9 bursts min -1 P = 0.03). Breathing 100% oxygen did not alter vascular sympathetic baroreflex function for either group at HA. For Lowlanders, upward baroreflex resetting promotes heightened sympathetic vasoconstrictor activity and maintains blood pressure stability, at least during early HA exposure; mechanisms other than peripheral chemoreflex activation could be involved. Sherpa adaptation appears to favour a lower sympathetic vasoconstrictor activity compared to Lowlanders for blood pressure homeostasis.

UR - https://physoc.onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1113%2FJP277663&file=tjp13483-sup-0001-Video.mp4

U2 - 10.1113/JP277663

DO - 10.1113/JP277663

M3 - Article

C2 - 30893472

VL - 597

SP - 2379

EP - 2390

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 9

ER -