Baroreflex control of sympathetic vasomotor activity and resting arterial pressure at high altitude: insight from Lowlanders and Sherpa

Abstract

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.

Keywords: Arterial baroreflex; Autonomic nervous system; High Altitude; Hypoxia; Sympathetic nerve activity; blood pressure.

Figure 1. Example Recordings of MSNA and BP

One representative Lowlander (aged 29 years) at LA (A), during acute hypoxia (B), following 8 days at HA (C), and during 100% oxygen breathing at HA (D). One representative Sherpa (aged 26 years) following 3 days at HA (E) and during 100% oxygen breathing at HA (F).

Figure 2. Vascular sympathetic baroreflex function

Group average regressions between MSNA burst probability and DBP in Lowlanders (n = 10) at 344 m (LA) and 5050 m (HA) and in Sherpa at HA (n = 7). The operating points are indicated by symbols and error bars (mean ± SD). The MSNA operating point was significantly elevated in Lowlanders at HA, relative to Lowlanders at LA. The MSNA operating point was lower in Sherpa relative to Lowlanders at HA, and similar to Lowlanders at LA. Operating DBP were similar. This indicated an upward resetting of the vascular sympathetic baroreflex following ascent to HA in Lowlanders. The slopes of the relationships were similar in Lowlanders at LA and HA (–2.3 ± 0.7 vs. –2.6 ± 1.2% mmHg⁻¹; P = 0.33) and similar in Sherpa at HA (–2.6 ± 0.9% mmHg⁻¹) compared to Lowlanders at both HA (P = 0.98) and LA (P = 0.99). This indicated that there were no differences in vascular sympathetic baroreflex gain. [Color figure can be viewed at wileyonlinelibrary.com]

Figure 3. Cardiovagal baroreflex function

Group average regressions between RRI and SBP in Lowlanders (n = 10) at 344 m (LA) and 5050 m (HA) and in native Sherpa at HA (n = 7). The operating points are indicated by symbols and error bars (mean ± SD). RRI significantly decreased in Lowlanders at HA, relative to Lowlanders at LA, although it was similar in Sherpa relative to Lowlanders at HA. Operating SBP were similar. This indicated a downward (RRI) resetting of the cardiovagal baroreflex in Lowlanders following ascent to HA. The slope of the relationship was less steep in Lowlanders at HA (16.2 ± 8.2 ms mmHg⁻¹) vs. LA (20.6 ± 5.0 ms mmHg⁻¹; P = 0.007), indicating a reduction in cardiovagal baroreflex gain following ascent to HA in Lowlanders. The slope of the relationship between SBP and RRI was similar in Sherpa at HA (12.9 ± 5.4 ms mmHg⁻¹; P = 0.60) relative to Lowlanders at HA, indicating no differences in reflex gain. Compared to Lowlanders at LA, operating SBP was similar but RRI was significantly smaller in Sherpa at HA, and the slope of the relationship was less steep (P = 0.01) [Color figure can be viewed at wileyonlinelibrary.com]