Tetrahydrobiopterin improves aging-related impairment of endothelium-dependent vasodilation through increase in nitric oxide production
Section snippets
Subjects
Thirty-seven healthy men (mean age, 41 ± 18 yr; range, 19–81 yr) were enrolled in this study. Subjects with a history of cardiovascular or cerebrovascular disease, hypertension, hypercholesterolemia, diabetes mellitus, liver disease, renal disease, or a smoking habit were excluded. The study protocol was approved by the Ethical Committee of the Hiroshima University School of Medicine. Informed consent for participation in this study was obtained from all subjects.
Study protocol: effects of BH4 on endothelium-dependent and -independent vasodilation
Forearm vascular responses to ACh
Clinical characteristics
The baseline clinical characteristics of the 37 healthy male subjects are shown in Table 1.
Effects of co-infusion of BH4 and ACh or ISDN on forearm hemodynamics
Intra-arterial infusions of ACh and ISDN significantly increased FBF in dose-dependent manners (Fig. 1, Fig. 2). The FBF response to ACh increased significantly with co-infusion of BH4 (Fig. 1). The increase in FBF during infusion of ISDN was not altered by co-infusion of BH4 (Fig. 2). No significant change was observed in arterial blood pressure or heart rate after intra-arterial infusion of either ACh
Discussion
The present findings demonstrate that BH4 augments ACh-induced vasodilation but not ISDN-induced vasodilation and that aging significantly correlated with FBF response to ACh, urinary excretion of 8-OHdG, serum concentration of MDA-LDL, and the augmentation of FBF response to ACH in combination with BH4. The infusion of l-NMMA completely abolished the enhancement of ACh-induced vasodilation by BH4.
In the present study, ACh-induced vasodilation was progressively more impaired with advance of
Acknowledgments
This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan, Japan Heart Foundation Grant for Research on Hypertension and Metabolism, and a Grant for Research Foundation for Community Medicine.
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