Chronic intermittent hypobaric hypoxia attenuates monocrotaline-induced pulmonary arterial hypertension via modulating inflammation and suppressing NF-κB /p38 pathway

Document Type: Original Article

Authors

1 Department of Heart Center, the First Hospital of Hebei Medical University, Shijiazhuang, 050031, China

2 Department of Endocrinology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050000, China

3 Department of Physiology, Foundation Medicine School of Hebei Medical University, Shijiazhuang, 050017, China

Abstract

Objective(s): Inflammation is involved in various forms of pulmonary arterial hypertension (PAH). Although the pathophysiology of PAH remains uncertain, NF-κB and p38 mitogen-activated protein kinase (p38 MAPK) has been reportedto be associated with many inflammatory mediators of PAH. This study aimed to evaluate the effect of chronic intermittent hypobaric hypoxia (CIHH) on pulmonary inflammation and remodeling in monocrotaline (MCT) induced PAH in rats.
Materials and Methods: An in vivo model of PAH induced by MCT was employed. Statistical analyses were assessed bydone using one-way analysis of variance (ANOVA) or Fisher's LSD test for multiple comparisons.
Results: Four weeks of CIHH exposure following MCT injection resulted in significant reduction of mean pulmonary artery pressure (mPAP) level and improvement of right ventricular hypertrophy (RVH). Morphometric analyses showed decreased wall thickness of pulmonary arterioles in MCT+CIHH treated rats. These findings are consistent with the decrease in Ki-67 immunostaining. Following CIHH treatments, apoptotic analysis showed a consistent decrease in T lymphocytes together with lower levels of CD4+ T cell subset as measured in spleen and blood samples. Furthermore, CIHH treatment resulted in markedly reduced expression of TNF-α and IL-6 via the inhibition of NF-κB and p38 MAPK activity in rat lungs.
Conclusion: Altogether, these results provide new evidence relating to the mode of action of CIHH in the prevention of PAH induced by MCT.

Keywords

Main Subjects


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