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Acute Tetrahydrobiopterin Improves Endothelial Function in Patients With COPD.
Rodriguez-Miguelez, Paula; Gregg, Justin; Seigler, Nichole; Bass, Leon; Thomas, Jeffrey; Pollock, Jennifer S; Sullivan, Jennifer C; Dillard, Thomas A; Harris, Ryan A.
Afiliación
  • Rodriguez-Miguelez P; Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA.
  • Gregg J; Pulmonary and Critical Care Medicine Department, Greenville Memorial Hospital, Greenville, SC.
  • Seigler N; Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA.
  • Bass L; Pulmonology Department, Holston Medical Group, Kingsport, TN.
  • Thomas J; Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA.
  • Pollock JS; Cardio-Renal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, AL.
  • Sullivan JC; Department of Physiology, Augusta University, Augusta, GA.
  • Dillard TA; Pulmonary and Critical Care, Department of Medicine, Augusta University, Augusta, GA.
  • Harris RA; Georgia Prevention Institute, Department of Pediatrics, Augusta University, Augusta, GA; Sport and Exercise Science Research Institute, Ulster University, Jordanstown, Northern Ireland. Electronic address: ryharris@augusta.edu.
Chest ; 154(3): 597-606, 2018 09.
Article en En | MEDLINE | ID: mdl-29705218
BACKGROUND: Cardiovascular diseases represent a hallmark characteristic in COPD, and endothelial dysfunction has been observed in these patients. Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide (NO) synthesis and a regulator of endothelial function. The goal of this study was to test the hypothesis that a single dose of BH4 would improve endothelial function in patients with COPD via an increase in NO bioavailability. METHODS: Seventeen patients with COPD completed a randomized, double-blind, placebo (PLC)-controlled, crossover trial with an acute dose of either BH4 (Kuvan; BioMarin Pharmaceutical Inc) or PLC. Flow-mediated dilation (FMD), a bioassay of endothelial function, was completed prior to and 3 h following each treatment. Phospho- and total endothelial NO synthase (NOS3) protein was evaluated after incubating endothelial cells with plasma from the patients prior to and following treatment. Fifteen demographically matched control subjects were tested at baseline for case control comparisons. RESULTS: Treatment with BH4 significantly (P ≤ .004) increased FMD, improving endothelial function in patients compared to control values (P ≥ .327). BH4 increased (P = .013) the ratio of phospho-NOS3 to total NOS3 protein. No changes in FMD (P ≥ .776) or the protein ratio (P = .536) were observed following PLC. CONCLUSIONS: An acute dose of BH4 was able to improve endothelial function in patients with COPD to values similar to control subjects. The improvement in endothelial function was accompanied by an increase in NOS3 phosphorylation. BH4 may represent a potential novel therapy to improve endothelial function and reduce cardiovascular disease risk in patients with COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01398943; URL: www.clinicaltrials.gov.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biopterinas / Endotelio Vascular / Óxido Nítrico Sintasa / Enfermedad Pulmonar Obstructiva Crónica / Óxido Nítrico Tipo de estudio: Clinical_trials Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Chest Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Biopterinas / Endotelio Vascular / Óxido Nítrico Sintasa / Enfermedad Pulmonar Obstructiva Crónica / Óxido Nítrico Tipo de estudio: Clinical_trials Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Chest Año: 2018 Tipo del documento: Article Pais de publicación: Estados Unidos