# Hydrogen rescues vascular endothelial cells in obstructive sleep apnea-hypopnea syndrome by modulating nitric oxide.
> 閉塞性睡眠時無呼吸低呼吸症候群における水素の血管内皮保護作用：一酸化窒素経路を介したメカニズムの解明


## Abstract

Obstructive sleep apnea-hypopnea syndrome (OSAHS) causes chronic intermittent hypoxia (IH), leading to oxidative stress and disrupted nitric oxide (NO) homeostasis that impairs vascular endothelial function. This study examined H2 effects using human umbilical vein endothelial cells exposed to IH cycles with 0.6 mM H2-rich medium, alongside a rat OSAHS model receiving 2% H2 inhalation for 1 hour daily over 4 weeks. H2 reduced ROS and malondialdehyde levels in both cellular and aortic tissue preparations. eNOS phosphorylation at Ser1177 was enhanced, and the BH4/BH2 ratio was preserved, preventing eNOS uncoupling and excess superoxide generation. Endothelium-dependent vasodilation improved in H2-treated rats. Additionally, vascular remodeling markers including medial thickening and collagen deposition were reduced, and inflammatory mediators TNF-α and ICAM-1 were downregulated. Endothelial apoptosis in aortic tissue also decreased significantly. These findings indicate that H2 restores NO bioavailability and exerts multi-target vascular protection in the context of OSAHS-related endothelial injury.

### Mechanism

H2 enhances eNOS phosphorylation at Ser1177 and preserves the BH4/BH2 ratio, preventing eNOS uncoupling and superoxide overproduction, thereby restoring NO bioavailability while concurrently suppressing oxidative stress, inflammatory signaling, and endothelial apoptosis.

## Bibliographic

- **Authors**: Chen Q, Jiang D, He J, Sun M
- **Journal**: J Thorac Dis
- **Year**: 2025 (2025-11-30)
- **PMID**: [41376930](https://pubmed.ncbi.nlm.nih.gov/41376930/)
- **DOI**: [10.21037/jtd-2025-1345](https://doi.org/10.21037/jtd-2025-1345)
- **PMC**: [PMC12688540](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12688540/)
- **Study type**: animal study
- **Delivery route**: mixed routes
- **Effect reported**: positive
- **H2 concentration**: 2%

## Delivery context

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

## Safety notes

This study combines multiple delivery routes. As a general principle, the most efficient route for routine hydrogen intake is inhalation. Inhalation carries explosion risk (empirical LFL of 10%; high-concentration devices are documented in the Consumer Affairs Agency accident database and are not recommended).

See also:
- [Inhalation concentration and LFL / UFL](https://h2-papers.org/en/safety-notes/inhalation-concentration)
- [Consumer Affairs Agency accident cases](https://h2-papers.org/en/safety-notes/accident-cases)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41376930. https://h2-papers.org/en/papers/41376930
> **Source**: PubMed PMID [41376930](https://pubmed.ncbi.nlm.nih.gov/41376930/)