Hypoxia in utero increases the risk of pulmonary hypertension in rat offspring and is associated with vasopressin type‑2 receptor upregulation

宫内缺氧会增加大鼠后代患肺动脉高压的风险,并与加压素 2 型受体上调有关

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作者:Hao Ding, Yuchuan Luo, Ke Hu, Huaying Huang, Pei Liu, Mengqing Xiong, Li Zhu, Jing Yi, Ying Xu

Abstract

Pulmonary hypertension (PH) in newborns and adults is a disease that can lead to right heart failure and result in a shorter lifespan. PH was induced by maintaining pregnant rats in a hypoxic chamber for 4 h twice a day, from days 7‑21 of pregnancy. Hypoxia was confirmed by a decrease in the partial pressure of oxygen (PaO2) and the oxygen saturation (SaO2) of arterial blood in the aorta. The body weight of newborns from hypoxic rats was ~20% decreased compared with the control newborns of normoxic rats. The vascular wall thickness/vascular diameter values of hypoxia treated pubs were increased compared with that of control newborns 7 days after birth; however, it decreased to similar levels than in the control group after 3 months, and then further decreased to significantly lower levels than in the control group at 6 months after birth. At birth, the lung tissues of newborns from hypoxic rats exhibited an increase in the levels of mRNA and proteins associated with PH such as HIF‑1α, HIF‑2α, V2R, TGF‑β, TNF‑α, Ang‑2 and α‑SMA. At 3 and 6 months after birth, the levels of both V2R mRNA and protein in offspring from hypoxic rats were at least 2‑fold higher, whereas the expression of all other factors decreased compared with the control offspring. By contrast, HIF‑2α and Ang‑2 expression levels were significantly increased in the 6‑month‑old control offspring from normoxic rats. V2R overexpression in pups induced by hypoxia in maternal rats was sustained until their adulthood. V2R may be a marker for detecting PH.

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