Rationale: Chronic exposure to hypoxia is associated with elevated sympathetic nervous activity and reduced vascular function in lowlanders, and Andean highlanders suffering from excessive erythrocytosis (EE); however, the mechanistic link between chronically elevated sympathetic nervous activity and hypoxia-induced vascular dysfunction has not been determined. Objective: To determine the impact of heightened sympathetic nervous activity on resistance artery endothelial-dependent dilation (EDD), and endothelial-independent dilation, in lowlanders and Andean highlanders with and without EE. Methods and Results: We tested healthy lowlanders (n=9) at sea level (344 m) and following 14 to 21 days at high altitude (4300 m), and permanent Andean highlanders with (n=6) and without (n=9) EE at high altitude. Vascular function was assessed using intraarterial infusions (3 progressive doses) of acetylcholine (ACh; EDD) and sodium nitroprusside (endothelial-independent dilation) before and after local α+β adrenergic receptor blockade (phentolamine and propranolol). Intraarterial blood pressure, heart rate, and simultaneous brachial artery diameter and blood velocity were recorded at rest and during drug infusion. Changes in forearm vascular conductance were calculated. The main findings were (1) chronic hypoxia reduced EDD in lowlanders (changes in forearm vascular conductance from sea level: ACh1: −52.7±19.6%, ACh2: −25.4±38.7%, ACh3: −35.1±34.7%, all P ≤0.02); and in Andeans with EE compared with non-EE (changes in forearm vascular conductance at ACh3: −36.4%, P =0.007). Adrenergic blockade fully restored EDD in lowlanders at high altitude, and normalized EDD between EE and non-EE Andeans. (2) Chronic hypoxia had no effect on endothelial-independent dilation in lowlanders, and no differences were detected between EE and non-EE Andeans; however, EID was increased in the non-EE Andeans after adrenergic blockade ( P =0.012), but this effect was not observed in the EE Andeans. Conclusions: These data indicate that chronic hypoxia reduces EDD via heightened α-adrenergic signaling in lowlanders and in Andeans with EE. These vascular mechanisms have important implications for understanding the physiological consequences of acute and chronic high altitude adaptation.

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High intensity interval training (HIIT) is widely used to improve VO2max. The purpose of this study was to examine if lower extremity HIIT resulted in improved maximal oxygen uptake (VO2max) and peak power output (PPO) of the upper extremities. Twenty healthy and trained participants (11 female and 9 male, VO2max 3160±1175 ml/min) underwent a 6-week HIIT program of the lower extremities on a cycle ergometer. Before and after the training period a maximal cycle ergometry (CE) and a maximal hand crank ergometry (HCE) were conducted to determine VO2max and PPO. Additionally, hematological parameters were determined. Increases in VO2max of the lower extremities (3160±1175 to 3449±1231 ml/min, p<0.001, η2p=0.779) as well as of the upper extremities (2255±938 to 2377±1015 ml/min, p=0.010, η2p=0.356) from pre- to post-test were found. PPO of the lower extremities increased (243±95 to 257±93 W, p<0.001, η2p=0.491), whereas it remained unchanged for the upper extremities (103±50 to 108±54 W, p=0.209, η2p=0.150). All hematological parameters increased. The results demonstrate that VO2max of the upper extremities increased after 6-weeks of cycling HIIT. However, upper body PPO was unchanged.

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Passive heating has emerged as a therapeutic intervention for the treatment and prevention of cardiovascular disease. Like exercise, heating increases peripheral artery blood flow and shear rate which is thought to be a primary mechanism underpinning endothelium mediated vascular adaptation. However, few studies have compared the increase in arterial blood flow and shear rate between dynamic exercise and passive heating. In a fixed crossover design study, 15 moderately trained healthy participants (25.6 ± 3.4 years) (5 female) underwent 30 minutes of whole body passive heating (42 °C bath), followed on a separate day by 30 minutes of semi-recumbent stepping exercise performed at two workloads corresponding to the increase in cardiac output (Qc) (Δ3.72 l∙min-1) and heart rate (HR) (Δ38 bpm) recorded at the end of passive heating. Results: At the same Qc (Δ3.72 l∙min-1 vs 3.78 l∙min-1), femoral artery blood flow (1599 ml/min vs 1947 ml/min) (p=0.596) and shear rate (162 s -1 vs 192 s-1) (p=0.471) measured by ultrasonography were similar between passive heating and stepping exercise. However, for the same HR matched intensity, femoral blood flow (1599 ml·min-1 vs 2588 ml·min-1) and shear rate (161s-1 vs 271s-1) were significantly greater during exercise, compared with heating (both P=<0.001). The results indicate that, for moderately trained individuals, passive heating increases common femoral artery blood flow and shear rate similar to low intensity continuous dynamic exercise (29% VO2max), however exercise performed at a higher intensity (53% VO2max) results in significantly larger shear rates towards the active skeletal muscle.