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

Michael M. Tymko, Joshua C. Tremblay, Alex B. Hansen, Connor A. Howe, Chris K. Willie, Mike Stembridge, Daniel J. Green, Ryan L. Hoiland, Prajan Subedi, James D. Anholm, Philip N. Ainslie

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    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.

    Original languageEnglish
    Pages (from-to)1671-1686
    Number of pages16
    JournalJournal of Physiology
    Volume595
    Issue number5
    DOIs
    Publication statusPublished - 1 Mar 2017

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    Tymko, M. M., Tremblay, J. C., Hansen, A. B., Howe, C. A., Willie, C. K., Stembridge, M., Green, D. J., Hoiland, R. L., Subedi, P., Anholm, J. D., & Ainslie, P. N. (2017). The effect of α1-adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude. Journal of Physiology, 595(5), 1671-1686. https://doi.org/10.1113/JP273183