Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis.
Clin Exp Rheumatol
; 35 Suppl 106(4): 167-172, 2017.
Article
in En
| MEDLINE
| ID: mdl-28980911
ABSTRACT
OBJECTIVES:
Systemic sclerosis (SSc) is a rare, autoimmune disease characterised by endothelial dysfunction, which is associated with peripheral vasculopathy, such as digital ulcers (DU). We sought to determine if acute oral administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase, would augment endothelial function in patients with SSc.METHODS:
Twelve SSc patients, of whom a majority had a history of DU, were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.RESULTS:
There were no differences in blood markers of oxidative stress and brachial artery blood pressure, diameter, blood velocity, shear rate, or blood flow at rest between placebo and BH4 (p>0.05). Whereas, after a 5 minute suprasystolic forearm cuff occlusion, brachial artery peak reactive hyperemia (placebo 313±30 vs. BH4 347±37 ml/min, p<0.05) and flow-mediated dilation (FMD) (placebo 3.0±0.8 vs. BH4 4.8±0.8%, p<0.05) were significantly higher after acute BH4 administration, indicating an improvement in endothelial function. To determine if the vasodilatory effects of BH4 were specific to the vascular endothelium, brachial artery blood flow and vasodilation in response to sublingual nitroglycerin were assessed, and were found to be unaffected by BH4 (p>0.05).CONCLUSIONS:
These findings indicate that acute BH4 administration ameliorates endothelial dysfunction in patients with SSc. Given that endothelial dysfunction is known to be associated with DU in SSc patients, this study provides a proof-of-concept for the potential therapeutic benefits of BH4 in the prevention or treatment of DU in this population.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Scleroderma, Systemic
/
Biopterins
/
Endothelium, Vascular
Type of study:
Clinical_trials
Limits:
Aged
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Clin Exp Rheumatol
Year:
2017
Document type:
Article
Affiliation country: