Mendes ES, Horvath G, Rebolledo P, Monzon ME, CasalinoMatsuda SM, Wanner A. Effect of an inhaled glucocorticoid on endothelial function in healthy smokers. J Appl Physiol 105: 54-57, 2008. First published May 8, 2008 doi:10.1152/japplphysiol.90334.2008.-Cigarette smoking is associated with attenuated endothelium-dependent vasodilation (endothelial dysfunction) in the systemic circulation, including the airway circulation. We wished to determine whether an inhaled corticosteroid could restore endothelial function in the airway of lung-healthy current smokers, ex-smokers, and nonsmokers. We measured baseline airway blood flow (Q aw) and Q aw reactivity to inhaled albuterol as an index of endothelium-dependent vasodilation and to sublingual nitroglycerin as an index of endothelium-independent vasodilation in lung-healthy current smokers, ex-smokers, and nonsmokers. Current smokers were then treated with inhaled fluticasone for 3 wk, and all measurements were repeated after fluticasone treatment and after a subsequent 3-wk fluticasone washout period. Baseline mean Q aw and endothelium-independent Q aw reactivity were similar in the three groups. Mean endothelium-dependent Q aw reactivity was 49.5% in nonsmokers, 42.7% in ex-smokers, and 10.8% in current smokers (P Ͻ 0.05 vs. nonsmokers). In current smokers, mean baseline Q aw was unchanged after fluticasone treatment, but endothelium-dependent Q aw reactivity significantly increased to 34.9%. Q aw reactivity was again blunted after fluticasone washout. Endothelial dysfunction, as assessed by vascular reactivity, can be corrected with an inhaled corticosteroid in the airway of lung-healthy current smokers. This proof of concept can serve as the basis for future clinical investigations on the effect of glucocorticoids on endothelial function in smokers.airway blood flow; smoking CIGARETTE SMOKING IS ASSOCIATED with attenuated vascular relaxation responses in the systemic circulation, and this defect has been related to cardiovascular disease (5, 30). The abnormal relaxation could be due to impaired vascular smooth muscle function or decreased stimulated endothelial nitric oxide (NO) release, a phenomenon that has been termed endothelial dysfunction. Impairments of both endotheliumindependent vascular relaxation (assessed with nitroglycerin) and endothelium-dependent vascular relaxation (assessed with a  2 -adrenergic agonist or flow-mediated vasodilation) have been reported, with the latter impairment being more consistent and of greater magnitude (1,5,31). Abnormal relaxation responses in smokers typically are demonstrated in the brachial artery, but other vascular beds, including the carotid and coronary arteries, are also involved, suggesting the presence of a global systemic vascular dysfunction (30, 31).The airway vasculature is derived from the systemic circulation and, therefore, participates in the vascular dysfunction seen in smokers. We have previously reported that healthy smokers have a blunted vasodilator response to inhaled albuterol in the airway as a...