scholarly journals Sildenafil improves vascular endothelial function in patients with cystic fibrosis

2018 ◽  
Vol 315 (5) ◽  
pp. H1486-H1494 ◽  
Author(s):  
Paula Rodriguez-Miguelez ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Gábor Csányi ◽  
Kathleen T. McKie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Endothelial Function ◽  
Protein Expression ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Systemic Complications ◽  
Acute Dose ◽  
Phosphodiesterase Type 5 Inhibitor ◽  
Before And After

Cystic fibrosis (CF), characterized by defective CFTR function, is associated with multiple systemic complications, including vascular dysfunction. Sildenafil, a phosphodiesterase type 5 inhibitor, not only enhances nitric oxide (NO) metabolism but has been shown to improve CFTR functionality as well. Thus, sildenafil has been proposed as a therapy to improve vascular health in CF; however, its potential therapeutic role has yet to be determined. We sought to investigate the effect of sildenafil on endothelial function in patients with CF. Patients with CF completed a randomized, double-blind, placebo-controlled, crossover study with an acute dose of sildenafil (50 mg) or placebo followed by a 4-wk open-label extension with sildenafil (20 mg/day). Flow-mediated dilation (FMD) was used to evaluate endothelial function before and after treatments. In addition, phosphorylated endothelial NO synthase (pNOS3) and total NOS3 protein expression was determined from endothelial cells that were exposed to plasma from the patients before and after 4 wk of sildenafil treatment. No changes ( P ≥ 0.110) in endothelial function were observed after the acute dose of sildenafil. However, FMD significantly ( P = 0.029) increased after 4 wk of treatment (∆FMD: 1.5 ± 2.2%). Moreover, pNOS3 protein expression significantly ( P = 0.013) increased after 4 wk of treatment (∆pNOS3: 0.31 ± 0.39 arbitrary units) and was associated ( r = 0.593, P = 0.033) with the change in FMD. These data suggest that 4 wk of sildenafil treatment can improve vascular endothelial function in patients with CF, likely through an increase in NOS3 phosphorylation. NEW & NOTEWORTHY Findings from the present study demonstrate, for the first time, significant improvement of endothelial function in patients with cystic fibrosis treated with sildenafil that is associated with greater phosphorylation of endothelial nitric oxide synthase. These results support the use of sildenafil as a potential novel therapy for this patient population.

scholarly journals Tetrahydrobiopterin improves endothelial function in patients with cystic fibrosis

2019 ◽  
Vol 126 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Jin Hee Jeong ◽  
Nichole Lee ◽  
Matthew A. Tucker ◽  
Paula Rodriguez-Miguelez ◽  
Jacob Looney ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cystic Fibrosis ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Function ◽  
Genetic Disorder ◽  
No Production ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
No Bioavailability

Cystic fibrosis (CF) is a genetic disorder associated with 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. Twenty-nine patients with CF (18 ± 8 yr old) and 29 healthy matched controls were recruited. Patients with CF participated in a randomized trial where they received 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 was retested following a placebo (PLC; n = 9). Brachial artery flow-mediated dilation (FMD) was used to evaluate vascular endothelial function, and a plasma sample was obtained before and 3 h after treatment. Cultured endothelial cells were treated with plasma to assess NO bioavailability. Baseline FMD was lower in patients compared with controls (5.7 ± 3.4 vs. 8.4 ± 3.5%, respectively, P = 0.005). No change in FMD was observed following PLC or BH4-5 (∆FMD: −0.8 ± 1.9% and −0.5 ± 2.5%; P = 0.273 and 0.132, respectively). Treatment with BH4-20, however, resulted in significant improvements in FMD (∆FMD: 1.1 ± 1.4%) compared with BH4-5 ( P = 0.023) and PLC ( P = 0.017). Moreover, BH4-20 significantly decreased endothelial cell superoxide production and increased NO production. These data suggest that a single oral dose of BH4 at 20 mg/kg improves vascular endothelial function in patients with CF, likely via increased endothelial NO synthase coupling. These findings support the hypothesis that loss of BH4 bioactivity contributes, in part, to endothelial dysfunction in patients with CF. NEW & NOTEWORTHY For the first time, the present study documents that a single dose of oral BH4 can improve vascular endothelial function in patients with cystic fibrosis (CF), and our in vitro data suggest this is via decreasing uncoupled nitric oxide. These data provide insight into the important role of BH4 bioactivity in vascular dysfunction and provide the foundation for further investigation into the chronic effects of BH4 treatment in patients with CF.

scholarly journals Changes in endothelial function during educational hospitalization and the contributor to improvement of endothelial function in type 2 diabetes mellitus

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yukiko Goshima ◽  
Yosuke Okada ◽  
Keiichi Torimoto ◽  
Yoshihisa Fujino ◽  
Yoshiya Tanaka
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Function ◽  
Multivariable Analysis ◽  
Vascular Endothelial ◽  
Single Factor ◽  
Vascular Endothelial Function ◽  
Before And After

Abstract Only a few reports have examined vascular endothelial function before and after educational hospitalization and the factors that affect it in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to assess vascular endothelial function before and after educational hospitalization and identify factors that affect it. In 65 patients with T2DM who underwent peripheral arterial tonometry (EndoPAT) before and after hospitalization, vascular endothelial function (reactive hyperemia index [RHI]), glucose metabolism, lipid metabolism, and blood pressure were assessed before and after hospitalization. The primary endpoint was hospitalization-induced changes in vascular endothelial function. Educational hospitalization significantly improved the natural logarithmically scaled RHI (L_RHI) from 0.555 ± 0.212 to 0.625 ± 0.245 (p = 0.012). Multivariable logistic regression analysis identified hypoglycemia during hospitalization as the single factor that significantly altered vascular endothelial function (p = 0.019). The odds of achieving normal vascular endothelial function were 0.08 times lower (95% confidence interval, 0.01–0.67) for each episode of hypoglycemia. Furthermore, multivariable analysis identified hypoglycemia during hospitalization as the single factor that worsened L_RHI. Our study showed that educational hospitalization of patients with T2DM improved vascular endothelial function, and that the development of hypoglycemic episodes had a significant negative impact on normalization of vascular endothelial function.

The effect of nitric oxide synthase 4ab gene polymorphism on vascular endothelial function in healthy subjects

2003 ◽  
Vol 12 (2) ◽  
pp. A55
Author(s):  
Bill Bilsborough ◽  
Daniel J. Green ◽  
Cyril D.S. Mamotte ◽  
Frank M. van Bockxmeer ◽  
Gerry O'Driscoll ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Gene Polymorphism ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Vascular Endothelial ◽  
Vascular Endothelial Function ◽  
Oxide Synthase

scholarly journals Influence of Cinepazide Maleate on Vascular Endothelial Function of Patients with Acute Myocardial Infarction

2015 ◽  
Vol 4 (3) ◽  
pp. 1
Author(s):  
Jiaming Niu ◽  
Zhaoling Ma
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Endothelial Function ◽  
Blood Serum ◽  
Control Group ◽  
Vascular Endothelial ◽  
Observation Group ◽  
Vascular Endothelial Function ◽  
Before And After ◽  
Better Than

<strong>Objective</strong>: To study influence of cinepazide maleate on vascular endothelial function of patients with acute myocardial infarction. <strong>Methods</strong>: 150 cases of patients with acute myocardial infarction were divided into the observation group and the control group, two groups were treated by conventional therapy about acute myocardial infarction, the observation group added 5%GS250 mL + cinepazide maleate 160 mg IV drip q.d, the control group added 5%GS250 mL IV drip q.d, the treatment course were 3 weeks, changes of vascular endothelial function and the blood serum no level before and after treatment were detected. <strong>Result</strong>: vascular endothelial function after treatment in observation group were obviously improved than that before treatment (<em>p</em> = 0.03) , blood serum no level was obviously increased (<em>p</em> ﹤ 0.05); about 3 weeks after treatment, vascular endothelial function in the observation group was obviously better than that of the control group (<em>p</em> = 0.04), the blood serum no level of the observation group was obviously higher than that of the control group (<em>p</em> ﹤ 0.05).<strong> Conclusion</strong>: Cinepazide maleate remarkably improves vascular endothelial function of patients with acute myocardial infarction.

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