Reactive oxygen species mediate functional differences in human radial and internal thoracic arteries from smokers

ObjectiveSmoking 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.MethodsIsometric tension was recorded on discarded segments of human left internal thoracic artery (ITA) and the radial artery (RA) from smokers and nonsmokers.ResultsThe 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°C. While during exposure to 28°C, basal fluorescence emission was unchanged in ITA rings, it increased significantly in RA rings, indicating enhanced formation of ROS in this peripheral artery.ConclusionsData 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.

Clinical RelevanceAttenuated responses to acetylcholine and enhanced production of reactive oxygen species in human radial arteries compared with internal mammary arteries have suggested that smoking induces endothelial dysfunction by increasing vascular reactive oxygen species production. Different levels of endogenous antioxidant enzyme activities in both arteries might be responsible for different functional changes. The present data suggest that the type of vessel chosen for coronary artery bypass grafting is important, and that especially in active smokers, radial artery conduits may lead to decreased graft patency and worse patient outcomes compared with internal thoracic artery conduits.