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

Abstract

Key Points Summary-Our objective was to quantify endothelial function (via brachial artery flow-mediated dilatation) at sea-level (344m) and high-altitude (3800m) at rest and following both maximal exercise and 30-minutes of moderate-intensity cycling exercise with and without administration of an 1-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-minutes of moderate-intensity exercise, and this decrease was abolished with 1-adrenergic blockade. At high-altitude, endothelial function did not decrease immediately post 30-minutes of moderate-intensity exercise, and administration of 1-adrenergic blockade resulted in an increase in flow mediated dilatation.-Our data indicates that post-exercise endothelial function is modified at high-altitude (i.e. prolonged hypoxemia). The current study helps elucidate the physiological mechanisms associated with high-altitude acclimatization, and provides insight into the relationship between sympathetic nervous activity and vascular endothelial function. AbstractWe 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 1-adrenergic pathway. In a double-blinded, counter-balanced, randomized and placebo-controlled design, nine healthy participants performed a maximal-exercise test, and two 30-minute sessions of semi-recumbent cycling exercise at 50% peak Watt following either placebo or 1-adrenergic blockade (prazosin; 0.05mg/kg). These experiments were completed at both sea-level (344m) and high-altitude (3800m). Blood pressure (finger photoplethysmography), heart rate (electrocardiogram), oxygen saturation (pulse oximetry), and brachial artery blood flow and shear rate (ultrasound) were recorded prior to, during, and following exercise. Endothelial function assessed by brachial artery flow-mediated dilatation (FMD) was measured prior to, immediately following, and 60-minutes post-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); 3) the 2.90.8% (P=0.043) reduction in FMD immediately after moderate-intensity exercise at sea-level was abolished via 1-adrenergic blockade. Conversely, at high-altitude, FMD was unaltered following moderate-intensity exercise, and administration of 1-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 hypoxemia on exercise...

One session of remote ischemic preconditioning does not improve vascular function in acute normobaric and chronic hypobaric hypoxia

“…; Tymko et al . ; Tremblay et al . ) or the presence of cardiovascular risk factors (Frøbert et al .…”

“…Two probable causes may contribute to this finding; either the duration or level of hypoxia was too small to elicit a reduction in FMD (measured after 15 min in acute hypoxia), or the magnitude of reduction in FMD was too small to identify with our sample size. There is emerging evidence that impairment in FMD is not a uniform response to hypoxia and may depend on severity, duration, concomitant exercise Tymko et al 2016b;Tremblay et al 2017) or the presence of cardiovascular risk factors (Frøbert et al 2008). In the present study, failure to alter FMD with RIPC could subsequently be explained by the lack of a meaningful vascular impairment in our model of hypoxia.…”

“…Remote ischemic preconditioning reduces oxidative stress after ischemic injuries (Chen et al 2015), and these same activated pathways might also attenuate the decline in vascular function at high altitude. Furthermore, RIPC has been demonstrated to preserve FMD immediately after strenuous exercise (Bailey et al 2012), a period that is normally associated with elevations in sympathetic nerve activity and a temporary impairment in vascular function Tymko et al 2016b).…”

The impact of hypoxaemia on vascular function in lowlanders and high altitude indigenous populations

“…Upon ascent to high altitude between 3800-5050 m, a decrease in endothelial function has been observed in most (Lewis et al 2014;Bakker et al 2015;Tymko et al 2017b;Tremblay et al 2018a,b), but not all studies (Bruno et al 2016;Tremblay et al 2017;Tymko et al 2017a). The disparity within the literature might be due to difference methodological approaches between investigations.…”

“…In contrast, the studies that reported no change in endothelial function involved participants without AMS ascending rapidly to high altitude via cable car (Bruno et al 2016), and healthy participants traveling to high altitude via automobile (studies part of the same research expedition; Tymko et al 2017a;Tremblay et al 2018b). The methodological difference between these studies raises the possibility of a moderating impact of trekking exercise at altitude, in addition to the severity of altitude exposure.…”