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J Am Coll Cardiol, 2000; 35:71-75
© 2000 by the American College of Cardiology Foundation
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Tetrahydrobiopterin restores endothelial function in long-term smokers

Seiji Ueda, MDa, Hidehiro Matsuoka, MD, PhDa, Hiroshi Miyazaki, MDa, Michiaki Usui, MDa, Seiya Okuda, MD, PhDa and Tsutomu Imaizumi, MD, PhD, FACCa

a Department of Internal Medicine III, and the Cardiovascular Research Institute, Kurume University School of Medicine, Kurume, Japan



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  		Figure 1 Effects of oral sapropterin hydrochloride, an active analogue of tetrahydrobiopterin, on flow-mediated (top) and GTN-induced (bottom) vasodilation in smokers and nonsmokers. Flow-mediated vasodilation of the brachial artery at baseline was significantly smaller in smokers (p = 0.0002). In smokers, sapropterin significantly augmented FMV (p < 0.0001 by post hoc analysis) but did not affect it in nonsmokers (smokers vs. nonsmokers, p = 0.001 for the interactions by ANOVA). Glyceryl trinitrate–induced vasodilation was not altered by sapropterin in smokers and nonsmokers.

 


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  		Figure 2 Effects of pretreatment with L-NMMA, a NOS inhibitor, on BH4-induced vasodilation in smokers. Infusion of L-NMMA into the brachial artery significantly decreased FMV in smokers (top) (p = 0.0008 by post hoc analysis), but did not affect GTN-induced vasodilation (bottom). The increase (top) (p = 0.0007 by post hoc analysis) in FMV induced by sapropterin 3 h after administration was abolished by pretreatment with L-NMMA (before vs. after sapropterin, p = 0.002 for the interactions by ANOVA).

 




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