Cerebrovascular Function in the Large Arteries Is Maintained Following Moderate Intensity Exercise.

Exercise has been shown to induce cerebrovascular adaptations. However, the underlying temporal dynamics are poorly understood, and regional variation in the vascular response to exercise has been observed in the large cerebral arteries. Here, we sought to measure the cerebrovascular effects of a single 20-min session of moderate-intensity exercise in the one hour period immediately following exercise cessation. We employed transcranial Doppler (TCD) ultrasonography to measure cerebral blood flow velocity (CBFV) in the middle cerebral artery (MCAv) and posterior cerebral artery (PCAv) before, during, and following exercise. Additionally, we simultaneously measured cerebral blood flow (CBF) in the internal carotid artery (ICA) and vertebral artery (VA) before and up to one hour following exercise cessation using Duplex ultrasound. A hypercapnia challenge was used before and after exercise to examine exercise-induced changes in cerebrovascular reactivity (CVR). We found that MCAv and PCAv were significantly elevated during exercise (p = 4.81 × 10-5 and 2.40 × 10-4, respectively). A general linear model revealed that these changes were largely explained by the partial pressure of end-tidal CO2 and not a direct vascular effect of exercise. After exercise cessation, there was no effect of exercise on CBFV or CVR in the intracranial or extracranial arteries (all p > 0.05). Taken together, these data confirm that CBF is rapidly and uniformly regulated following exercise cessation in healthy young males.

UBC-Nepal Expedition: acute alterations in sympathetic nervous activity do not influence brachial artery endothelial function at sea level and high altitude.

Evidence indicates that increases in sympathetic nervous activity (SNA), and acclimatization to high altitude (HA), may reduce endothelial function as assessed by brachial artery flow-mediated dilatation (FMD); however, it is unclear whether such changes in FMD are due to direct vascular constraint, or consequential altered hemodynamics (e.g., shear stress) associated with increased SNA as a consequence of exposure to HA. We hypothesized that 1) at rest, SNA would be elevated and FMD would be reduced at HA compared with sea-level (SL); and 2) at SL and HA, FMD would be reduced when SNA was acutely increased, and elevated when SNA was acutely decreased. Using a novel, randomized experimental design, brachial artery FMD was assessed at SL (344 m) and HA (5,050 m) in 14 participants during mild lower-body negative pressure (LBNP; -10 mmHg) and lower-body positive pressure (LBPP; +10 mmHg). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (Duplex ultrasound) were recorded during LBNP, control, and LBPP trials. Muscle SNA was recorded (via microneurography) in a subset of participants (n = 5). Our findings were 1) at rest, SNA was elevated (P < 0.01), and absolute FMD was reduced (P = 0.024), but relative FMD remained unaltered (P = 0.061), at HA compared with SL; and 2) despite significantly altering SNA with LBNP (+60.3 ± 25.5%) and LBPP (-37.2 ± 12.7%) (P < 0.01), FMD was unaltered at SL (P = 0.448) and HA (P = 0.537). These data indicate that acute and mild changes in SNA do not directly influence brachial artery FMD at SL or HA.NEW & NOTEWORTHY The role of the sympathetic nervous system on endothelial function remains unclear. We used lower-body negative and positive pressure to manipulate sympathetic nervous activity at sea level and high altitude and measured brachial endothelial function via flow-mediated dilation. We found that acutely altering sympathetic nervous activity had no effect on endothelial function.

Adenosine receptor-dependent signaling is not obligatory for normobaric and hypobaric hypoxia-induced cerebral vasodilation in humans.

Hypoxia increases cerebral blood flow (CBF) with the underlying signaling processes potentially including adenosine. A randomized, double-blinded, and placebo-controlled design, was implemented to determine if adenosine receptor antagonism (theophylline, 3.75 mg/Kg) would reduce the CBF response to normobaric and hypobaric hypoxia. In 12 participants the partial pressures of end-tidal oxygen ([Formula: see text]) and carbon dioxide ([Formula: see text]), ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), CBF (duplex ultrasound), and intracranial blood velocities (transcranial Doppler ultrasound) were measured during 5-min stages of isocapnic hypoxia at sea level (98, 90, 80, and 70% [Formula: see text]). Ventilation, [Formula: see text] and [Formula: see text], blood pressure, heart rate, and CBF were also measured upon exposure (128 ± 31 min following arrival) to high altitude (3,800 m) and 6 h following theophylline administration. At sea level, although the CBF response to hypoxia was unaltered pre- and postplacebo, it was reduced following theophylline (P < 0.01), a finding explained by a lower [Formula: see text] (P < 0.01). Upon mathematical correction for [Formula: see text], the CBF response to hypoxia was unaltered following theophylline. Cerebrovascular reactivity to hypoxia (i.e., response slope) was not different between trials, irrespective of [Formula: see text] At high altitude, theophylline (n = 6) had no effect on CBF compared with placebo (n = 6) when end-tidal gases were comparable (P > 0.05). We conclude that adenosine receptor-dependent signaling is not obligatory for cerebral hypoxic vasodilation in humans.NEW & NOTEWORTHY The signaling pathways that regulate human cerebral blood flow in hypoxia remain poorly understood. Using a randomized, double-blinded, and placebo-controlled study design, we determined that adenosine receptor-dependent signaling is not obligatory for the regulation of human cerebral blood flow at sea level; these findings also extend to high altitude.

The effect of α1 -adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.

KEY POINTS: Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea level (344 m) and high altitude (3800 m) at rest and following both maximal exercise and 30 min of moderate-intensity cycling exercise with and without administration of an α1 -adrenergic blockade. Brachial endothelial function did not differ between sea level and high altitude at rest, nor following maximal exercise. At sea level, endothelial function decreased following 30 min of moderate-intensity exercise, and this decrease was abolished with α1 -adrenergic blockade. At high altitude, endothelial function did not decrease immediately after 30 min of moderate-intensity exercise, and administration of α1 -adrenergic blockade resulted in an increase in flow-mediated dilatation. Our data indicate that post-exercise endothelial function is modified at high altitude (i.e. prolonged hypoxaemia). The current study helps to elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. ABSTRACT: We examined the hypotheses that (1) at rest, endothelial function would be impaired at high altitude compared to sea level, (2) endothelial function would be reduced to a greater extent at sea level compared to high altitude after maximal exercise, and (3) reductions in endothelial function following moderate-intensity exercise at both sea level and high altitude are mediated via an α1 -adrenergic pathway. In a double-blinded, counterbalanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30 min sessions of semi-recumbent cycling exercise at 50% peak output following either placebo or α1 -adrenergic blockade (prazosin; 0.05 mg kg -1 ). These experiments were completed at both sea-level (344 m) and high altitude (3800 m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded before, during and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured before, immediately following and 60 min after exercise. Our findings were: (1) at rest, FMD remained unchanged between sea level and high altitude (placebo P = 0.287; prazosin: P = 0.110); (2) FMD remained unchanged after maximal exercise at sea level and high altitude (P = 0.244); and (3) the 2.9 ± 0.8% (P = 0.043) reduction in FMD immediately after moderate-intensity exercise at sea level was abolished via α1 -adrenergic blockade. Conversely, at high altitude, FMD was unaltered following moderate-intensity exercise, and administration of α1 -adrenergic blockade elevated FMD (P = 0.032). Our results suggest endothelial function is differentially affected by exercise when exposed to hypobaric hypoxia. These findings have implications for understanding the chronic impacts of hypoxaemia on exercise, and the interactions between the α1 -adrenergic pathway and endothelial function.