title: The effect of α1-adrenergic blockade on post-exercise brachial artery flow-mediated dilatation at sea level and high altitude.
abstract: 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.
  
  
  
  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.
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Michael M
authors.identifier: 0000-0001-9945-339X
authors.initials: MM
authors.lastname: Tymko
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Tremblay
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Alex B
authors.initials: AB
authors.lastname: Hansen
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Connor A
authors.initials: CA
authors.lastname: Howe
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Chris K
authors.initials: CK
authors.lastname: Willie
authors.affiliation: Cardiff School of Sport, Cardiff Metropolitan University, Cardiff, UK.
authors.forename: Mike
authors.initials: M
authors.lastname: Stembridge
authors.affiliation: School of Sports Science, Exercise and Health, The University of Western Australia, Crawley, Western Australia, Australia.|Research Institute for Sport and Exercise Science, Liverpool John Moores University, Liverpool, UK.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Ryan L
authors.identifier: 0000-0002-5657-0059
authors.initials: RL
authors.lastname: Hoiland
authors.affiliation: Pulmonary/Critical Care Section, Medical Service, VA Loma Linda Healthcare System, Loma Linda, CA, USA.
authors.forename: Prajan
authors.initials: P
authors.lastname: Subedi
authors.affiliation: Pulmonary/Critical Care Section, Medical Service, VA Loma Linda Healthcare System, Loma Linda, CA, USA.
authors.forename: James D
authors.initials: JD
authors.lastname: Anholm
authors.affiliation: Centre for Heart, Lung, and Vascular Health, School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ainslie
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D000531:Altitude; D001916:Brachial Artery / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D015444:Exercise / Q000502:physiology*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D011224:Prazosin / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D011224:Prazosin
keywords: endothelial function; exercise; flow-mediated dilatation; high-altitude; sympathetic nervous activity