Constitutive hydrogen inhalation prevents vascular remodeling via reduction of oxidative stress.

Abstract

C57BL/6 mice inhaled 1.3% hydrogen gas (O2 21%, N2 77.7%) continuously for two weeks starting at 8 weeks of age, after which femoral artery injury was induced by polyethylene cuff placement. Hydrogen inhalation was maintained until tissue collection. Neointima formation accompanied by elevated cell proliferation was significantly reduced in hydrogen-exposed animals relative to air-only controls. NADPH oxidase subunit NOX1 expression was downregulated in the hydrogen group following cuff injury, whereas p40phox and p47phox levels did not differ significantly between groups. Superoxide anion production showed no significant intergroup difference; however, DNA damage was markedly reduced, attributed to decreased levels of hydroxyl radicals and peroxynitrite. These findings indicate that sustained low-concentration hydrogen inhalation attenuates vascular remodeling partly through selective scavenging of highly reactive oxygen species, pointing to a potential preventive role against conditions such as atherosclerosis.

Mechanism

Inhaled hydrogen selectively scavenges hydroxyl radicals and peroxynitrite, downregulates NADPH oxidase NOX1 expression, reduces DNA damage, and thereby suppresses neointimal hyperplasia following vascular injury.