Tetrahydrobiopterin Improves Endothelial Function in Patients with Cystic Fibrosis

Jinhee Jeong, Nicole Lee, Matthew Tucker, Paula Rodriguez Miguelez, Jacob Looney, Jeffrey Thomas, Casandra Derella, Ahmed Elmarakby, Jacqueline Musall, Jennifer Sullivan, Kathleen McKie, Caralee Forseen, Gareth Davison, Ryan Harrie

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9 Citations (Scopus)
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Cystic fibrosis (CF) is a genetic disorder associated with a wide range of systemic complications, including vascular endothelial dysfunction. Nitric oxide (NO) plays a major role in maintaining vascular function and tetrahydrobiopterin (BH4) is a critical determinant of NO bioavailability. Thus, the purpose of this study was to investigate the effects of oral administration of BH4 on endothelial function in patients with CF. Methods: 29 patients with CF (18 ± 8 yrs old) and 29 healthy matched controls were recruited. Patients with CF participated in a randomized trial where they received either a 5 mg/kg dose of oral BH4 (BH4-5; n=17) or a 20 mg/kg dose of oral BH4 (BH4-20; n=12). On a separate visit, a subset of patients from each group were retested following a placebo (PLC, n=9). Brachial artery flow-mediated dilation (FMD) was used to evaluate vascular endothelial function before and 3 h after treatment. Results: Baseline FMD was lower in patients compared to controls. No change in FMD was observed following either PLC or BH4-5 (∆FMD: -0.8 ± 0.0% and -0.5 ± 2.5%; p=0.273 and 0.132, respectively). Treatment with BH4-20, however, resulted in a significant improvement in FMD (∆FMD: 1.1 ± 1.4%) when compared to BH4-5 (p=0.023) and PLC (p=0.017). Conclusion: These data suggest that a single oral dose of BH4 at 20 mg/kg can improve vascular endothelial function in patients with CF. These findings support the hypothesis that BH4 bioactivity contributes, in part, to endothelial dysfunction in patients with CF.
Original languageEnglish
Pages (from-to)60-66
Number of pages7
JournalJournal of Applied Physiology
Early online date15 Nov 2018
Publication statusPublished (in print/issue) - 31 Jan 2019


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