title: Reactive oxygen species mediate functional differences in human radial and internal thoracic arteries from smokers.
abstract: OBJECTIVE
  Smoking not only increases the risk that coronary heart disease will develop but also morbidity and mortality in patients with known coronary atherosclerosis and after coronary artery bypass grafting. Excessive generation of reactive oxygen species (ROS) has been implicated as the final common pathway for the development of endothelial dysfunction in various cardiovascular risk factors. This study assessed the influence of smoking on two different human arteries routinely used as coronary artery bypass graft conduits.
  
  
  METHODS
  Isometric tension was recorded on discarded segments of human left internal thoracic artery (ITA) and the radial artery (RA) from smokers and nonsmokers.
  
  
  RESULTS
  The contractile response to endothelin-1 was significantly stronger in arteries from smokers than in those from nonsmokers. By contrast, endothelium-dependent relaxant responses to acetylcholine were attenuated in RA rings but enhanced in ITA rings from smokers. In additional experiments, 5-(&6)-chloromethyl-2'-7'-dichlorodihydro-fluorescein diacetate (DCDHF) was used to photochemically detect ROS by confocal imaging of intact ITA and RA. Enhanced production of ROS was induced by exposure of tissues to 28 degrees C. While during exposure to 28 degrees C, basal fluorescence emission was unchanged in ITA rings, it increased significantly in RA rings, indicating enhanced formation of ROS in this peripheral artery.
  
  
  CONCLUSIONS
  Data suggest that smoking induces endothelial dysfunction by increasing vascular ROS production. Different levels of endogenous antioxidant enzyme activities and the degree of atherosclerotic changes might modulate physiologic and pharmacologic vasoreactivity and be responsible for decreased graft patency of RA compared with ITA conduits, especially in active smokers.
authors.affiliation: Heart Surgery Center Basel-Bern, University Hospital, Bern, Switzerland. dremueller@bluewin.ch
authors.forename: Else
authors.initials: E
authors.lastname: Müller-Schweinitzer
authors.forename: Sandra E
authors.initials: SE
authors.lastname: Müller
authors.forename: David C
authors.initials: DC
authors.lastname: Reineke
authors.forename: Thomas
authors.initials: T
authors.lastname: Kern
authors.forename: Thierry P
authors.initials: TP
authors.lastname: Carrel
authors.forename: Friedrich S
authors.initials: FS
authors.lastname: Eckstein
authors.forename: Martin T R
authors.initials: MT
authors.lastname: Grapow
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000368:Aged; D001026:Coronary Artery Bypass; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D018613:Microscopy, Confocal; D008875:Middle Aged; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D018384:Oxidative Stress; D017534:Radial Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D017382:Reactive Oxygen Species; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D000109:Acetylcholine; D009638:Norepinephrine