Chronic Normobaric Hypoxia Induces Pulmonary Hypertension in Rats: Role of NF-κB

High Altitude Medicine & Biology
Junming FanYongsheng Gong

Abstract

To investigate whether nuclear factor-kappa B (NF-κB) activation is involved in chronic normobaric hypoxia-induced pulmonary hypertension (PH), rats were treated with saline or an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC, 150 mg/kg, sc, twice daily), and exposed to normoxia or chronic normobaric hypoxia with a fraction of inspired oxygen of ∼0.1 for 14 days. Lung tissue levels of NF-κB activity, and interleukin (IL)-1β, IL-6, and cyclooxygenase-2 mRNAs, were determined, and mean pulmonary arterial pressure, right ventricular hypertrophy, and right heart function were evaluated. Compared to the normoxia exposure group, rats exposed to chronic normobaric hypoxia showed an increased NF-κB activity, measured by increased nuclear translocation of p50 and p65 proteins, an increased inflammatory gene expression in the lungs, elevated mean pulmonary arterial blood pressure and mean right ventricular pressure, right ventricular hypertrophy, as assessed by right ventricle-to-left ventricle plus septum weight ratio, and right heart dysfunction. Treatment of hypoxia-exposed rats with PDTC inhibited NF-κB activity, decreased pulmonary arterial blood pressure and right ventricular pressure, and ameliorated right ventricular hypertr...Continue Reading

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Citations

Sep 22, 2018·Journal of Cellular Physiology·Krishnamurthy NakuluriAnil Kumar Pasupulati
Jul 7, 2017·Pulmonary Circulation·Abubakr ChaudhryC Michael Hart
Mar 11, 2020·Frontiers in Endocrinology·Jiri Pavlacky, Jan Polak
Jul 3, 2021·Cells·Lukas RoubenneChristelle Guibert
Jul 28, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Qiuyun TianYongsheng Gong

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Methods Mentioned

BETA
ubiquitination
PCR
Protein Assay
nuclear translocation

Software Mentioned

GraphPad
Prism
ImageJ System

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