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

Abstract

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.

Keywords: endothelial function; exercise; flow-mediated dilatation; high-altitude; sympathetic nervous activity.

Figure 1. FMD data collected during baseline on placebo and prazosin at sea level and high altitude

White bars represent sea‐level data ± SEM, and black bars represent high‐altitude data ± SEM in nine participants. FMD, flow‐mediated dilatation. These findings illustrate that there were no differences in resting FMD between sea level and high altitude after passive ascent to 3800 m.

Figure 2. Cardiovascular data during baseline, maximal exercise and post‐maximal exercise at sea level and high altitude

Open circles represent sea‐level data ± SEM, and closed circles high‐altitude data ± SEM in nine participants. ^* P < 0.05, for interaction effects. Statistics for main effects and interactions are displayed on the top right of each panel. BL, baseline; Max‐Ex, maximal exercise; Post‐Max, post‐maximal exercise; $S_{\mathrm{p}{\mathrm{O}}_2}$, per cent oxygen saturation of haemoglobin; SV, stroke volume, HR, heart rate; CO, cardiac output; MAP, mean arterial pressure; TPR, total peripheral resistance. Collectively, these findings reveal that SV, HR, CO and $S_{\mathrm{p}{\mathrm{O}}_2}$ were all elevated at sea level compared to high altitude during a maximal exercise test.

Figure 3. Individual FMD data collected at baseline and post‐maximal exercise at sea level and high altitude

Mean data (n = 9) are represented by the grey line plot. BL, baseline; Post‐Max, post‐maximal exercise; FMD, flow‐mediated dilatation. These data reveal that we found no change in FMD at post‐maximal exercise at sea level and high altitude.

Figure 4. Cardiovascular data during baseline, moderate‐intensity exercise and post‐exercise time‐points on placebo and prazosin at sea level and high altitude

Open circles represent placebo data ± SEM, and closed circles represent prazosin data ± SEM in nine participants. ^* P < 0.05, for interaction effects. Statistics for main effects and interactions are displayed on the top right of each panel. BL, baseline; Post, immediately after exercise; Post 60, 60 min after exercise; $S_{\mathrm{p}{\mathrm{O}}_2}$, per cent oxygen saturation of haemoglobin; SV, stroke volume, HR, heart rate; CO, cardiac output; MAP, mean arterial pressure; TPR, total peripheral resistance. These findings demonstrate that, at sea level, SV was elevated, while HR was reduced on placebo compared to prazosin during 30 min of moderate‐intensity exercise. At high altitude, $S_{\mathrm{p}{\mathrm{O}}_2}$ and HR were lower, while MAP and HR were higher on placebo compared to prazosin during 30 min of moderate‐intensity exercise.

Figure 5. Brachial artery shear rate data during baseline, moderate‐intensity exercise and post‐exercise time‐points on placebo and prazosin at sea level and high altitude

Open circles represent placebo data ± SEM, and closed circles represent prazosin data ± SEM in nine participants. ^* P < 0.05, for interaction effects. Statistics for main effects and interactions are displayed on the top right of each panel. BL, baseline; Post, immediately after exercise; Post 60, 60 min after exercise. These data reveal that retrograde shear rate was greater after prazosin administration at sea level, while at high altitude, mean and antegrade shear rate were greater after prazosin administration compared to placebo during 30 min of moderate‐intensity exercise.

Figure 6. Brachial artery velocity, diameter, blood flow and conductance data collected during baseline, moderate‐intensity exercise and post‐exercise time‐points on placebo and prazosin at sea level and high altitude

Open circles represent placebo data ± SEM, and closed circles represent prazosin data ± SEM in nine participants. ^* P < 0.05, for interaction effects. Statistics for main effects and interactions are displayed on the top right of each panel. BL, baseline; Post, immediately after exercise; Post 60, 60 min after exercise. These findings illustrate that there were no differences found in brachial artery velocity, diameter, blood flow and conductance at sea level between placebo and prazosin trials; however, at high altitude, we found brachial artery velocity, blood flow and conductance were reduced while participants were on placebo compared to prazosin during the 30 min moderate‐intensity exercise test.

Figure 7. Individual FMD data collected during baseline and post‐exercise time‐points on placebo and prazosin at sea level and high altitude

Mean data (n = 9) are represented by the grey line plot. ^* P < 0.05, represents time effect, where FMD Post‐EX was lower compared to baseline, and Post‐60 (for more details, see Results section). Post, immediately after exercise; Post 60, 60 min after exercise; FMD, flow‐mediated dilatation. Collectively, these findings reveal that at sea level, FMD was reduced immediately after 30 min of moderate‐intensity exercise while on placebo, and the reduction in FMD was abolished after administration of prazosin. At high altitude, there was no observed reduction in FMD immediately after 30 min of moderate‐intensity exercise after administration of placebo or prazosin. Additionally, after taking into account changes in brachial baseline diameter and shear rate between placebo and prazosin trials, FMD was elevated after administration of prazosin compared to placebo at high altitude.