Oxidative stress and local inflammation in rat adrenal medulla in chronic hypoxia

Abstract

BACKGROUND: Chronic hypoxia (CH) leads to cardiopulmonary changes in subjects sojourning at high altitude, and pathophysiological changes in patients with chronic obstructive pulmonary disease. Sympathetic activation of the adrenal medulla plays an important role in the cardiovascular response to hypoxia. Oxidative stress triggered by a variety of stimuli including hypoxia can mediate cellular damages with increased productions of reactive oxygen species and free radicals in local tissues. HYPOTHESIS: oxidative stress induced by CH, leads to local inflammation and cellular injury in the rat adrenal medulla. METHODS: Normoxic (N) and CH rats were exposed to air and 10% O2 for 7 days, respectively. The adrenal medulla was harvested for the measurement of markers for oxidative stress, malondialdhyde (MDA) and nitrotyrosine (NTR), and for the histological analysis of macrophages infiltration and TUNEL staining for apoptosis. Also, the expressions of NADPH oxidase subunits p22phox and NOX-4 were examined by RT-PCR. RESULTS: The MDA level was significantly increased in the CH group, when compared with the Nx control. Image analysis also showed significantly more % adrenal medulla area with positive immunostaining of NTR than that of the Nx group. In addition, macrophage marker ED1-immunoreactivity was remarkable in the CH group, suggesting a local inflammation. Also, there was an increase in apoptotic cells in the adrenal medulla of CH rats. Moreover, the mRNA expression of p22phox was increased in the CH group, suggesting an involvement of NADPH oxidase in the oxidative stress. SUMMARY: Results support our hypothesis that CH-induced oxidative stress is involved in the local inflammation and apoptosis in the adrenal medulla. The role of the NADPH oxidase in the CH-induced oxidative stress awaits further investigation.