Elevated levels of fibrinogen, C-reactive protein, and increased platelet aggregation are known to be increased by cigarette smoking, but the underlying mechanisms of the prothrombotic state in smokers are not completely understood. Since cigarette smoke contains several oxidants, we investigated the effect of the antioxidant ascorbic acid on stimulated fibrinolytic activity in smokers. Long-term heavy smokers and nonsmokers were studied by measurement of forearm blood flow; coinfusion of ascorbic acid was used to reduce oxidative stress. Concentrations of t-PA antigen and activity, of plasminogen activator inhibitor-1 (PAI-1) antigen and activity, and of C-reactive protein were determined by enzyme-linked immunosorbent assays and photometry, respectively. While dose-response curves of forearm blood flow elicited by substance P were not altered by the coadministration of ascorbic acid in nonsmokers, impaired flow in smokers markedly increased, P=0.003. Also, selectively in smokers, the maximal stimulated net release of t-PA antigen and of t-PA activity increased when ascorbic acid was infused simultaneously, P=0.002. In smokers CRP concentrations correlated significantly with the effect of ascorbic acid on maximal t-PA activity release, P
