# Molecular Hydrogen Modulates the Baroreflex Activity and Reduces the Vascular Adrenoreceptor Sensitivity to Phenylephrine and Lung Inflammation in Rats with Pulmonary Hypertension.
> 肺高血圧ラットにおける分子状水素の圧受容器反射活性・血管アドレナリン受容体感受性・肺炎症への影響


## Abstract

Using a monocrotaline-induced pulmonary hypertension (MCT) model in male Wistar rats, this study examined the cardiovascular and vascular effects of 4% H2 inhalation administered twice daily for 2 hours over 21 days. In awake animals, the heart rate increase following nitroprusside-induced hypotension was significantly lower in the MCT-H2 group (48.1 ± 10.2 beats/min) compared with the MCT-Air group (73.1 ± 16.7 beats/min; p < 0.01), indicating modulation of baroreflex sensitivity. In isolated aortic preparations from MCT rats, adding H2 to the perfusion medium reduced the maximal contractile response to the α-adrenoceptor agonist phenylephrine by approximately 30% and decreased its potency (EC50) threefold. Vasodilatory responses to nitroprusside and acetylcholine were also assessed. Additionally, reduced tryptase secretion in lung tissue pointed to an anti-inflammatory action of H2. These findings collectively indicate that H2 inhalation attenuates autonomic cardiovascular regulation and peripheral vascular adrenergic reactivity in pulmonary hypertension.

### Mechanism

H2 selectively scavenges hydroxyl radicals and peroxynitrite while suppressing inflammatory cytokine synthesis, thereby reducing α-adrenoceptor-mediated vascular contractility and modulating baroreflex-driven heart rate responses in pulmonary hypertension.

## Bibliographic

- **Authors**: Artemieva M, Kozaeva L, Kuropatkina T, Gufranov K, Atiakshin D, Medvedeva N, et al.
- **Journal**: Biomedicines
- **Year**: 2026 (2026-02-24)
- **PMID**: [41898141](https://pubmed.ncbi.nlm.nih.gov/41898141/)
- **DOI**: [10.3390/biomedicines14030494](https://doi.org/10.3390/biomedicines14030494)
- **PMC**: [PMC13023450](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13023450/)
- **Study type**: animal study
- **Delivery route**: inhalation
- **Effect reported**: positive
- **H2 concentration**: 4%

## Delivery context

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information database and are not recommended.

## Safety notes

For inhalation applications of molecular hydrogen, the lower flammability limit (LFL) deserves careful handling. The classical 4% figure applies to closed-system mixtures; the practical inhalation-environment threshold is 10%. Even pure-hydrogen output (the UFL 75% paradox) passes through the flammable range at the air–gas boundary. High-concentration (66% / 100%) inhalers are documented in the Japanese Consumer Affairs Agency accident-information 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)
- [LFL / UFL terminology](https://h2-papers.org/en/safety-notes/lfl-ufl-explained)
- [Inhalation safety threshold lineage](https://h2-papers.org/en/safety-notes/lineage)

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> **Cite as**: H2 Papers — PMID 41898141. https://h2-papers.org/en/papers/41898141
> **Source**: PubMed PMID [41898141](https://pubmed.ncbi.nlm.nih.gov/41898141/)