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Decreased Kv1.5 expression in intrauterine growth retardation rats with exaggerated pulmonary hypertension.

Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(11):L856-65. Epub 2013 Sep 27
Ying Lv 1 , Li-Li Tang , Jia-Kai Wei , Xue-Feng Xu , Weizhong Gu , Lin-Chen Fu , Li-Yan Zhang , Li-Zhong Du
Ying Lv 1 , Li-Li Tang , Jia-Kai Wei , Xue-Feng Xu , Weizhong Gu , Lin-Chen Fu , Li-Yan Zhang , Li-Zhong Du
+ et al

[No authors listed]

Author information
  • 1 The Children's Hospital, Zhejiang Univ. School of Medicine, Hangzhou, Zhejiang province, P.R. China, 310003. dulizhong@zju.edu.cn.

摘要


Chronic hypoxia pulmonary hypertension (CH-PHT) in adulthood is likely to be of fetal origin following intrauterine growth retardation (IUGR). Oxygen (O₂)-sensitive voltage-gated potassium channels (Kv channels) in resistance pulmonary artery smooth muscle cells (PASMCs) play an important role in scaling pulmonary artery (PA) pressure. Expression and functional changes of Kv channels are determined, in part, by embryonic development. We hypothesized that O₂-sensitive Kv channels play an important role in exaggerated CH-PHT following IUGR. We established a rat model of IUGR by restricting maternal food during the entire pregnancy and exposed IUGR rats and their age-matched controls aged 12 wk to hypoxia for 2 wk. We found that hypoxia exposure significantly induced increased PA pressure and thicker smooth muscle layer in the IUGR group relative to controls. We compared the constriction of the resistance PA to inhibitors of K⁺ channels, 4-aminopyridine (4-AP), tetraethylammonium, and BaCl₂. Despite the thickness of the smooth muscle layer, the constriction to 4-AP was significantly reduced in the IUGR group exposed to hypoxia. Consistent with these changes in pulmonary vascular reactivity, 2 wk of hypoxia induced weaker 4-AP-sensitive Kv currents in a single IUGR PASMC. Moreover, after 2 wk of hypoxia, Kv1.5 expression in resistance PAs decreased significantly in the IUGR group. Overexpression of Kv1.5 in cultured PASMCs could offset hypoxia-induced cell proliferation and hypoxia-inhibited Kv currents in the IUGR group. These results suggest that the inhibited expression of Kv1.5 in PASMCs contribute to the development of exaggerated CH-PHT in IUGR rats during adulthood.

KEYWORDS: chronic hypoxic pulmonary hypertension, intrauterine growth retardation, pulmonary artery smooth muscle cell, voltage-gated potassium channel