title: Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease.
abstract: BACKGROUND
  In patients with stable coronary artery disease, physical exercise training (ET) improves endothelial dysfunction. A potential mechanism mediating the enhanced vasomotor function is a reduced breakdown of endothelium-derived nitric oxide by reactive oxygen species (ROS). The aim of the present study was to analyze the impact of ET on sources of ROS generation in the left internal mammary artery of patients with symptomatic coronary artery disease.
  
  
  RESULTS
  In left internal mammary artery rings sampled during bypass surgery from 45 patients randomized to either a training (n=22) or an inactive control (n=23) group, the mRNA expression of NAD(P)H oxidase subunits, NAD(P)H oxidase activity, and ROS production were assessed. In addition, endothelial function, expression of angiotensin II (Ang II) receptor type 1 and 2 (AT1-R and AT2-R), and Ang II-mediated vasoconstriction were determined. ET resulted in a significant lower expression of gp91phox (23.1+/-0.5 versus 69.1+/-18.1 arbitrary units, training versus control), p22phox (0.7+/-0.3 versus 2.0+/-0.5 arbitrary units), and Nox4 (2.7+/-1.2 versus 5.4+/-1.0 arbitrary units). Enzymatic activity (2.1+/-0.3 versus 4.9+/-0.4 mU/mg) and ROS generation (0.02+/-0.01 versus 0.06+/-0.02 arbitrary units) were significantly lower in the training compared with the control group. On a functional level, ET resulted in improved acetylcholine-mediated vasodilatation and a 49% reduction in Ang II-induced vasoconstriction, accompanied by lower AT1-R (3.7+/-0.8 versus 16.6+/-5.7 arbitrary units, training versus control) and higher AT2-R (7.8+/-2.5 versus 1.6+/-0.7 arbitrary units) mRNA expression.
  
  
  CONCLUSIONS
  ET reduces vascular expression of NAD(P)H oxidase and AT1-R, resulting in decreased local ROS generation. These molecular effects converge in a reduced Ang II-mediated vasoconstriction.
authors.affiliation: University Leipzig, Heart Center Leipzig, Department of Cardiology, Leipzig, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Adams
authors.forename: Axel
authors.initials: A
authors.lastname: Linke
authors.forename: Nicolle
authors.initials: N
authors.lastname: Kränkel
authors.forename: Sandra
authors.initials: S
authors.lastname: Erbs
authors.forename: Stephan
authors.initials: S
authors.lastname: Gielen
authors.forename: Sven
authors.initials: S
authors.lastname: Möbius-Winkler
authors.forename: Jan F
authors.initials: JF
authors.lastname: Gummert
authors.forename: Friedrich Wilhelm
authors.initials: FW
authors.lastname: Mohr
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schuler
authors.forename: Rainer
authors.initials: R
authors.lastname: Hambrecht
mesh_terms: D000368:Aged; D000804:Angiotensin II / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000201:enzymology / Q000378:metabolism* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology; D015444:Exercise; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
chemical_list: D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014662:Vasoconstrictor Agents; D013481:Superoxides; D000804:Angiotensin II; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases