Abstract
Background
The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical.
Objectives
To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, H2, can be a useful modulator of blood vessel function.
Methods
The efficacy of water containing a high concentration of H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high-H2 group, who drank high-H2 water containing 7 ppm H2 (3.5 mg H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high-H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline.
Results
FMD increased in the high-H2 group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (P<0.05) in the high-H2 group compared to the placebo group.
Conclusion
H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.
Acknowledgments
We thank M Hanada and K Nagao for the technical support. We are grateful to R Kurokawa, S Hirano, T Seo, M Nagao, K Kiyota, and K Fukuoka for their excellent advice on the preparation of placebo water.
Author contributions
All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in either drafting the article or revising it critically for important intellectual content; gave final approval of the version to be published.
Disclosure
The authors report no conflicts of interest in this work.