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Article

Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection

  • Authors:
    • Rong Zhu
    • Li‑Qing Bi
    • Su‑Ling Wu
    • Lan Li
    • Hui Kong
    • Wei-Ping Xie
    • Hong Wang
    • Zi-Li Meng
  • View Affiliations / Copyright

    Affiliations: Department of Respiratory Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Geriatric Intensive Care Unit, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Respiratory Medicine, The Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
  • Pages: 2945-2952
    |
    Published online on: April 28, 2015
       https://doi.org/10.3892/mmr.2015.3695
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Abstract

The present study aimed to investigate the protective effects of iptakalim, an adenosine triphosphate (ATP)-sensitive potassium channel opener, on the inflammation of the pulmonary artery and endothelial cell injury in a hypoxia‑induced pulmonary arterial hypertension (PAH) rat model. Ninety‑six Sprague‑Dawley rats were placed into normobaric hypoxia chambers for four weeks and were treated with iptakalim (1.5 mg/kg/day) or saline for 28 days. The right ventricle systolic pressures (RVSP) were measured and small pulmonary arterial morphological alterations were analyzed with hematoxylin and eosin staining. Enzyme‑linked immunosorbent assay (ELISA) was performed to analyze the content of interleukin (IL)‑1β and IL‑10. Immunohistochemical analysis for ED1+ monocytes was performed to detect the inflammatory cells surrounding the pulmonary arterioles. Western blot analysis was performed to analyze the expression levels of platelet endothelial cell adhesion molecule‑1 (PECAM‑1) and endothelial nitric oxide synthase (eNOS) in the lung tissue. Alterations in small pulmonary arteriole morphology and the ultrastructure of pulmonary arterial endothelial cells were observed via light and transmission electron microscopy, respectively. Iptakalim significantly attenuated the increase in mean pulmonary artery pressure, RVSP, right ventricle to left ventricle plus septum ratio and small pulmonary artery wall remodeling in hypoxia‑induced PAH rats. Iptakalim also prevented an increase in IL‑1β and a decrease in IL‑10 in the peripheral blood and lung tissue, and alleviated inflammatory cell infiltration in hypoxia‑induced PAH rats. Furthermore, iptakalim enhanced PECAM‑1 and eNOS expression and prevented the endothelial cell injury induced by hypoxic stimuli. Iptakalim suppressed the pulmonary arteriole and systemic inflammatory responses and protected against the endothelial damage associated with the upregulation of PECAM‑1 and eNOS, suggesting that iptakalim may represent a potential therapeutic agent for PAH.
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Copy and paste a formatted citation
Spandidos Publications style
Zhu R, Bi LQ, Wu SL, Li L, Kong H, Xie W, Wang H and Meng Z: Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection. Mol Med Rep 12: 2945-2952, 2015.
APA
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W. ... Meng, Z. (2015). Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection. Molecular Medicine Reports, 12, 2945-2952. https://doi.org/10.3892/mmr.2015.3695
MLA
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W., Wang, H., Meng, Z."Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection". Molecular Medicine Reports 12.2 (2015): 2945-2952.
Chicago
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W., Wang, H., Meng, Z."Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection". Molecular Medicine Reports 12, no. 2 (2015): 2945-2952. https://doi.org/10.3892/mmr.2015.3695
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu R, Bi LQ, Wu SL, Li L, Kong H, Xie W, Wang H and Meng Z: Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection. Mol Med Rep 12: 2945-2952, 2015.
APA
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W. ... Meng, Z. (2015). Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection. Molecular Medicine Reports, 12, 2945-2952. https://doi.org/10.3892/mmr.2015.3695
MLA
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W., Wang, H., Meng, Z."Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection". Molecular Medicine Reports 12.2 (2015): 2945-2952.
Chicago
Zhu, R., Bi, L., Wu, S., Li, L., Kong, H., Xie, W., Wang, H., Meng, Z."Iptakalim attenuates hypoxia-induced pulmonary arterial hypertension in rats by endothelial function protection". Molecular Medicine Reports 12, no. 2 (2015): 2945-2952. https://doi.org/10.3892/mmr.2015.3695
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