Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects

Abstract

Objective: The pathogenesis of pulmonary arterial hypertension (PAH) involves reactive oxygen species and inflammation. Beneficial effects of molecular hydrogen, which exerts both anti-inflammatory and antioxidative effects, have been reported for various pathologic conditions. We therefore hypothesized that molecular hydrogen would improve monocrotaline (MCT)-induced PAH in rats. Methods: Nineteen male Sprague-Dawley rats (body weight: 200-300 g) were divided into groups, receiving: (1) MCT þ hydrogen-saturated water (group H); (2) MCT þ dehydrogenized water (group M); or (3) saline þ dehydrogenized water (group C). Sixteen days after substance administration, we evaluated hemodynamics, harvested the lungs and heart, and performed morphometric analysis of the pulmonary vasculature. Macrophage infiltration, antiproliferating cell nuclear antigen–positive cells, 8-hydroxy-deoxyguanosine (8-OHdG)–positive cells, and expressions of phosphorylated signal transducers and activators of transcription-3 (STAT3) and nuclear factor of activated T-cells (NFAT) were evaluated immunohistochemically. Stromal cell–derived factor-1 and monocyte chemoattractant protein-1 expressions were evaluated by quantitative reverse-transcription polymerase chain reaction. Results: Pulmonary arterial hypertension was significantly exacerbated in group M compared to group C, but was significantly improved in group H. Vascular density was significantly reduced in group M, but not in group H. Adventitial macrophages, antiproliferating cell nuclear antigen - and 8-OHdG–positive cells, and stromal cell–derived factor-1 and monocyte chemoattractant protein-1 expressions were significantly increased in group M, but improved in group H. Expressions of phosphorylated STAT3 and NFAT were up-regulated in group M, but improved in group H. Conclusions: Molecular hydrogen ameliorates MCT-induced PAH in rats by suppressing macrophage accumulation, reducing oxidative stress and modulating the STAT3/NFAT axis.

Study details

Article type

Original Research

Disease / injury model

Monocrotaline-induced pulmonary arterial hypertension (PAH) in rats

Duration

16 days

Dose-dependent effect

No

Outcome

Positive

Findings

Molecular hydrogen ameliorates monocrotaline-induced pulmonary arterial hypertension (PAH) in rats by suppressing macrophage accumulation, reducing oxidative stress, and modulating the STAT3/NFAT axis. Hydrogen-saturated water improved right ventricular systolic pressure, reduced right ventricular hypertrophy, decreased muscularization of pulmonary arteries, reduced smooth muscle cell proliferation, increased vascular density, and reduced markers of inflammation and oxidative stress.