α-Adrenergic regulation of blood pressure in acclimatizing lowlanders and Andean highlanders at high altitude

Elevated muscle sympathetic nerve activity (MSNA) at high altitude is associated with blunted transduction of sympathetic signals to blood pressure in lowlanders and indigenous Andean highlanders. However, it is unclear whether this is due to reduced adrenergic communication or other factors (e.g., augmented dilatory signaling). Therefore, we quantified the contribution of α-adrenoreceptor activity to 1) resting systemic sympathetic transduction and 2) pressor responses to sympathoexcitation in acclimatizing lowlanders (9 M and 4 F) and Andean highlanders (15 M) at 4,300 m. MSNA (microneurography) and mean arterial pressure (MAP; finger photoplethysmography) were measured at rest, during maximal voluntary apnea, and with an α₁-adrenergic agonist (phenylephrine) before and following partial α-adrenergic blockade (phentolamine). Sympathetic transduction was quantified as the slope of the relationship between MAP and total MSNA associated with sequences of sympathetic bursts. Transduction was attenuated in both lowlanders (0.0041 ± 0.0037 to 0.0017 ± 0.0017 mmHg·%^-1, P = 0.026) and highlanders (0.0033 ± 0.0024 to 0.0008 ± 0.0007 mmHg·%^-1, P = 0.005) under α-adrenergic blockade (main effect P < 0.001) and was not different between groups (main effect P = 0.276). However, pressor responses to apnea (lowlanders, +25 ± 5 mmHg and highlanders, +22 ± 7 mmHg) were unchanged following phentolamine (lowlanders, +25 ± 8 mmHg and highlanders, +20 ± 8 mmHg; main effect P = 0.174) despite unchanged MSNA responses between conditions (main effect P = 0.162). Highlanders exhibited reduced MSNA responses compared with lowlanders regardless of condition (main effect P = 0.014). Partial α-adrenergic blockade reduced sympathetic transduction similarly in both groups. Yet, apnea responsiveness was maintained, achieved through lesser sympathoexcitation in highlanders. This suggests that resting blood pressure control is modulated primarily through α-adrenergic receptors in both populations, but pressor responses to stress may result from alternative mechanisms.NEW & NOTEWORTHY This study provides insight into the mechanisms involved in the sympathetic control of blood pressure at rest and in response to autonomic stress in different populations at high altitude. We demonstrate that resting blood pressure regulation is mediated primarily through α-adrenergic mechanisms in both lowlanders and Indigenous Andean highlanders at high altitude. However, pressor responses to apneic stress appear to be regulated by an alternative mechanism, particularly in highlanders who require less sympathetic activation.