title: Alpha adrenergic receptor blockade increases capillarization and fractional O2extraction and lowers blood flow in contracting human skeletal muscle.
abstract: OBJECTIVE
  To assess the effect of elevated basal shear stress on angiogenesis in humans and the role of enhanced skeletal muscle capillarization on blood flow and O2extraction.
  
  
  METHODS
  Limb haemodynamics and O2extraction were measured at rest and during one-leg knee-extensor exercise (12 and 24 W) in 10 healthy untrained young men before and after 4-week treatment with an α1receptor-antagonist (Terazosin, 1-2 mg day-1). Corresponding biopsies were taken from the m. vastus lateralis.
  
  
  RESULTS
  Resting leg blood flow was increased by 57% 6 h following Terazosin treatment (P < 0.05), while basal capillary-to-fibre ratio was 1.69 ± 0.08 and increased to 1.90 ± 0.08 after treatment (P < 0.05). Leg O2extraction during knee-extensor exercise was higher (4-5%; P < 0.05), leg blood flow and venous lactate levels lower (6-7%; P < 0.05), while leg VO2was not different after Terazosin treatment.
  
  
  CONCLUSIONS
  These results demonstrate that daily treatment with an α-adrenergic receptor blocker induces capillary growth in human skeletal muscle, likely due to increased shear stress. The increase in capillarization resulted in an increased fractional O2extraction, a lower blood flow and venous lactate levels in the exercising leg. The increase in capillarization, and concomitant functional readouts in the exercising leg, may provide a basis for novel angiotherapy.
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.|Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
authors.forename: S P
authors.initials: SP
authors.lastname: Mortensen
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds, UK.
authors.forename: S
authors.initials: S
authors.lastname: Egginton
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Madsen
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
authors.forename: J B
authors.initials: JB
authors.lastname: Hansen
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: G D W
authors.initials: GDW
authors.lastname: Munch
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: U W
authors.initials: UW
authors.lastname: Iepsen
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Åkerström
authors.affiliation: The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
authors.affiliation: Department of Nutrition, Exercise and Sport, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Y
authors.initials: Y
authors.lastname: Hellsten
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D000328:Adult; D006439:Hemodynamics / Q000502:physiology*; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D011224:Prazosin / Q000031:analogs & derivatives / Q000494:pharmacology; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; C041226:Terazosin; D011224:Prazosin
keywords: capillarization; skeletal muscle; vasodilatation