Vascular endothelial function and oxidative stress mechanisms in patients with Behçet’s syndrome

OBJECTIVES We sought to test the hypothesis that vascular endothelial function is impaired in Behçet’s syndrome and reflects increased levels of oxidative stress. BACKGROUND Behçet’s syndrome is a multisystem inflammatory disorder commonly complicated by vascular thrombosis and arterial aneurysm formation. The precise mechanisms underlying vascular disease in Behçet’s syndrome are not known. METHODS We studied 19 patients with Behçet’s syndrome (18 to 50 years old, 9 men) and 21 healthy volunteers (18 to 50 years old, 10 men). Brachial artery flow-mediated dilation (endothelium-dependent), and nitroglycerin (NTG)-induced dilation (endothelium-independent) were measured. To investigate oxidative stress mechanisms, vascular studies were repeated 1 h after administration of vitamin C (1 g, intravenous) in 12 patients and 12 control subjects. RESULTS Flow-mediated dilation was reduced in patients with Behçet’s syndrome as compared with control subjects (0.7 ± 0.9% vs. 5.7 ± 0.9%, P = 0.001). In contrast, there were no significant differences in the brachial artery diameter (4.2 ± 0.2 vs. 4.0 ± 0.2 mm, P = 0.47) or NTG-induced dilation (19.7 ± 1.9% vs. 19.7 ± 1.2%, P = 0.98). In regression analysis, Behçet’s syndrome was associated with impaired flow-mediated dilation independent of age, gender, brachial artery diameter, blood pressure, cholesterol and glucose. Vitamin C increased flow-mediated dilation in Behçet’s syndrome (0.2 ± 0.7% to 3.5 ± 1.0%, P = 0.002), but not in control subjects (4.3 ± 0.6% to 4.7 ± 0.4%, P = 0.51). In both groups, NTG-induced dilation and brachial artery diameter were unchanged after vitamin C treatment. CONCLUSIONS Vascular endothelial function is impaired in Behçet’s syndrome and can be rapidly improved by vitamin C treatment. Our results support a role for oxidative stress in the pathophysiology of Behçet’s syndrome and provide a rationale for therapeutic studies aimed at reducing vascular complications in this disorder.