title: Vasoactive enzymes and blood flow responses to passive and active exercise in peripheral arterial disease.
abstract: BACKGROUND
  Peripheral arterial disease (PAD) is characterised by impaired leg blood flow, which contributes to claudication and reduced exercise capacity. This study investigated to what extent vasoactive enzymes might contribute to altered blood flow in PAD (Fontaine stage II).
  
  
  METHODS
  We compared femoral artery blood flow during reactive hyperaemia, leg-extension exercise and passive leg movement, and determined the level of vasoactive enzymes in skeletal muscle samples from the vastus lateralis in PAD (n = 10, 68.5 ± 6.5 years) and healthy controls (CON, n = 9, 62.1 ± 12.3 years). Leg blood flow was measured with Doppler ultrasound and muscle protein levels of phosphorylated endothelial nitric oxide synthase, NADPH oxidase, cyclooxygenase 1 and 2, thromboxane synthase, and prostacyclin synthase were determined.
  
  
  RESULTS
  Leg blood flow during the initial 90 s of passive leg movement (242 ± 33 vs 441 ± 75 ml min(-1), P = 0.03) and during reactive hyperaemia (423 ± 100 vs 1255 ± 175 ml min(-1), P = 0.002) was lower in PAD than CON, whereas no significant difference was observed for leg blood flow during exercise (1490 ± 250 vs 1887 ± 349 ml min(-1), P = 0.37). PAD had higher NADPH oxidase than CON (1.04 ± 0.19 vs 0.50 ± 0.06 AU, P = 0.02), with no differences for other enzymes. Leg blood flow during exercise was correlated with prostacyclin synthase (P = 0.001).
  
  
  CONCLUSIONS
  Elevated NADPH oxidase indicates that oxidative stress may be a primary cause of low nitric oxide availability and impaired blood flow in PAD.
authors.affiliation: School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia. Electronic address: mwalker@usc.edu.au.
authors.forename: Meegan A
authors.initials: MA
authors.lastname: Walker
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. Electronic address: bhoier@nexs.ku.dk.
authors.forename: Birgitte
authors.initials: B
authors.lastname: Hoier
authors.affiliation: School of Medicine, Royal Brisbane and Women's Hospital, University of Queensland, Herston, Queensland, Australia.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Walker
authors.affiliation: Sunshine Vascular Surgery and Imaging, Buderim, Queensland, Australia.
authors.forename: Karl
authors.initials: K
authors.lastname: Schulze
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. Electronic address: jbangsbo@nexs.ku.dk.
authors.forename: Jens
authors.initials: J
authors.lastname: Bangsbo
authors.affiliation: Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark. Electronic address: yhellsten@nexs.ku.dk.
authors.forename: Ylva
authors.initials: Y
authors.lastname: Hellsten
authors.affiliation: School of Health and Sport Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia. Electronic address: caskew@usc.edu.au.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Askew
mesh_terms: D000368:Aged; D055109:Ankle Brachial Index; D001783:Blood Flow Velocity; D016022:Case-Control Studies; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015444:Exercise; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology*; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D019255:NADPH Oxidases / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D058729:Peripheral Arterial Disease / Q000175:diagnosis / Q000201:enzymology* / Q000503:physiopathology; D010766:Phosphorylation; D052097:Quadriceps Muscle / Q000201:enzymology*; D012039:Regional Blood Flow; D013930:Thromboxane-A Synthase / Q000378:metabolism; D013997:Time Factors; D018608:Ultrasonography, Doppler
chemical_list: D003577:Cytochrome P-450 Enzyme System; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D019255:NADPH Oxidases; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013930:Thromboxane-A Synthase
keywords: Leg blood flow; NADPH oxidase; Peripheral arterial disease; Vasoactive enzymes