Highs and Lows of Sympathetic Neuro-cardiovascular Transduction: Influence of Altitude Acclimatization and Adaptation: Phenotypic differences in neuro-cardiovascular transduction

High-altitude (>2500m) exposure results in increased muscle sympathetic nervous activity (MSNA) in acclimatizing lowlanders. However, little is known about how altitude affects MSNA in indigenous high-altitude populations. Additionally, the relationship between MSNA and blood pressure regulation (i.e., neurovascular transduction) at high-altitude is unclear. We sought to determine 1) how high-altitude effects neuro-cardiovascular transduction and 2) whether differences exist in neuro-cardiovascular transduction between low and high-altitude populations. Measurements of MSNA (microneurography), mean arterial blood pressure (MAP; finger photoplethysmography), and heart rate (electrocardiogram) were collected in: I) lowlanders (n=14) at low (344m) and high-altitude (5050m), II) Sherpa highlanders (n=8; 5050m), and III) Andean (with and without excessive erythrocytosis) highlanders (n=15; 4300m). Cardiovascular responses to MSNA burst sequences (i.e. singlet, couplet, triplet, and quadruplets) were quantified using custom software (coded in MATLAB, v2015b). Slopes were generated for each individual based on peak responses and normalized total MSNA. High altitude reduced neuro-cardiovascular transduction in lowlanders (MAP slope: high-altitude, 0.0075±0.0060 vs low-altitude, 0.0134±0.080; p=0.03). Transduction was elevated in Sherpa (MAP slope, 0.012±0.007) compared to Andeans (0.003±0.002; p=0.001). MAP transduction was not statistically different between acclimatizing lowlanders and Sherpa (MAP slope, p=0.08) or Andeans (MAP slope, p=0.07). When accounting for resting MSNA (ANCOVA), transduction was inversely related to basal MSNA (bursts/min) independent of population (RRI, r= 0.578 p<0.001; MAP, r= -0.627 p<0.0001). Our results demonstrate transduction is blunted in individuals with higher basal MSNA, suggesting blunted neuro-cardiovascular transduction is a physiological adaptation to elevated MSNA rather than an effect or adaptation specific to chronic hypoxic exposure.