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Effect of NADPH oxidase inhibitor apocynin on the expression of hypoxia-induced factor-1α and endothelin-1 in rat carotid body exposed to chronic intermittent hypoxia

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The effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor apocynin on the enhanced hypoxia induced factor-1α (HIF-1α) and endothelin-1 (ET-1) expression, elevated systolic blood pressure under chronic intermittent hypoxia (CIH) condition and its action mechanism were investigated. Thirty healthy 8-week old Sprague-Dawley (SD) male rats were randomly divided into three groups (n=10 each): sham group, CIH group, and apocynin-treated CIH group. Tail artery systolic blood pressure was measured by tail-cuff method. Real-time fluorescence quantitative polymerase chain reaction (PCR) was used to detect the mRNA expression of HIF-1α and ET-1 in the carotid body, and the HIF-1α protein expression was examined by using Western blotting. The levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were determined by using colorimetric method. In addition, the plasma ET-1 and HIF-1α levels were measured by using enzyme-linked immunosorbent assay. It was found that CIH exposure was associated with increased MDA levels, and apocynin-treated CIH animals showed reduction in MDA levels. Apocynin treatment prevented CIH-induced hypertension as well as CIH-induced decrease in SOD. The increases of HIF-1α and ET-1 mRNA along with HIF-1α protein expression in the carotid body, and elevated circulating HIF-1α and ET-1 levels were observed in CIH-exposed animals. Treatment with apocynin significantly decreased the ET-1 mRNA, HIF-1α protein expression and circulating HIF-1α level in CIH-exposed animals, and there was no statistically significant difference in the HIF-1α mRNA expression between CIH group and apocynin-treated group. These results indicated that apocynin alleviated CIH-induced hypertension by inhibiting NADPH oxidase, further leading to the reduced vasoconstrictor ET-1 level and oxidative stress. HIF-1α/ET-1 system signal pathway may interact with CIH-induced NADPH oxidase-dependent oxidative stress. Inhibition of NADPH oxidase activity may hopefully serve as a useful strategy for prevention and treatment of obstructive sleep apnea hypopnea syndrome-induced hypertension.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Respiratory Disease of The Ministry of Health, Wuhan, 430030, China

    Xue Liu  (刘 雪), Yan Deng  (邓 燕), Jin Shang  (尚 进), Xiu-hong Yang  (杨秀红), Kui Liu  (刘 馗), Hui-guo Liu  (刘辉国) & Yong-jian Xu  (徐永健)

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  1. Xue Liu  (刘 雪)
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  2. Yan Deng  (邓 燕)
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  3. Jin Shang  (尚 进)
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  4. Xiu-hong Yang  (杨秀红)
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  5. Kui Liu  (刘 馗)
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  6. Hui-guo Liu  (刘辉国)
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Correspondence to Hui-guo Liu  (刘辉国) or Yong-jian Xu  (徐永健).

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The authors contributed equally to this work.

This project was supported by the National Natural Science Foundation of China (No. 81070067).

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Liu, X., Deng, Y., Shang, J. et al. Effect of NADPH oxidase inhibitor apocynin on the expression of hypoxia-induced factor-1α and endothelin-1 in rat carotid body exposed to chronic intermittent hypoxia. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 33, 178–184 (2013). https://doi.org/10.1007/s11596-013-1093-z

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  • DOI: https://doi.org/10.1007/s11596-013-1093-z

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