Gestational hypoxia adversely affects uterine artery function, increasing complications. However, an effective therapy remains unidentified. Here, we show in rodent uterine arteries that hypoxic pregnancy promotes hypertrophic remodelling, increases constrictor reactivity via protein kinase C signalling, and triggers compensatory dilatation via nitric oxide-dependent mechanisms and stimulation of large conductance Ca²⁺-activated K⁺-channels. Maternal in vivo oral treatment with the mitochondria-targeted antioxidant MitoQ in hypoxic pregnancy normalises uterine artery reactivity and prevents vascular remodelling. From days 6–20 of gestation (term ∼22 days), female Wistar rats were randomly assigned to normoxic or hypoxic (13–14% O₂) pregnancy ± daily maternal MitoQ treatment (500 µm in drinking water). At 20 days of gestation, maternal, placental and fetal tissue was frozen to determine MitoQ uptake. The uterine arteries were harvested and, in one segment, constrictor and dilator reactivity was determined by wire myography. Another segment was fixed for unbiased stereological analysis of vessel morphology. Maternal administration of MitoQ in both normoxic and hypoxic pregnancy crossed the placenta and was present in all tissues analysed. Hypoxia increased uterine artery constrictor responses to norepinephrine, angiotensin II and the protein kinase C activator, phorbol 12,13-dibutyrate. Hypoxia enhanced dilator reactivity to sodium nitroprusside, the large conductance Ca²⁺-activated K⁺-channel activator NS1619 and ACh via increased nitric oxide-dependent mechanisms. Uterine arteries from hypoxic pregnancy showed increased wall thickness and MitoQ treatment in hypoxic pregnancy prevented all effects on uterine artery reactivity and remodelling. The data support mitochondria-targeted therapy against adverse changes in uterine artery structure and function in high-risk pregnancy.

妊娠期缺氧会对子宫动脉功能产生不利影响，增加并发症。然而，有效的治疗方法仍未确定。在这里，我们在啮齿动物子宫动脉中发现，缺氧妊娠促进肥厚性重塑，通过蛋白激酶 C 信号传导增加缩窄反应性，并通过一氧化氮依赖性机制和刺激大电导 Ca ²⁺激活 K ⁺通道触发代偿性扩张。在缺氧妊娠中，母亲体内口服线粒体靶向抗氧化剂 MitoQ 可以使子宫动脉反应正常化，并防止血管重塑。从妊娠第 6-20 天（足月~22 天）起，雌性 Wistar 大鼠被随机分配至正常含氧量或低氧量 (13-14% O ₂ ) 妊娠±每日母体 MitoQ 治疗组（500 µm饮用水中）。妊娠 20 天时，冷冻母体、胎盘和胎儿组织以确定 MitoQ 的吸收。收获子宫动脉，并通过钢丝肌动描记术测定一段子宫动脉的收缩器和扩张器反应性。固定另一段用于血管形态的无偏立体学分析。在常氧和缺氧妊娠中，母体给予 MitoQ 会穿过胎盘并存在于所有分析的组织中。缺氧会增加子宫动脉收缩肌对去甲肾上腺素、血管紧张素 II 和蛋白激酶 C 激活剂佛波醇 12,13-二丁酸酯的反应。缺氧通过增加一氧化氮依赖性机制增强了扩张剂对硝普钠、大电导 Ca ²⁺激活的 K ⁺通道激活剂 NS1619 和 ACh 的反应性。缺氧妊娠的子宫动脉显示壁厚增加，缺氧妊娠的 MitoQ 治疗可防止对子宫动脉反应性和重塑的所有影响。这些数据支持针对高危妊娠中子宫动脉结构和功能不良变化的线粒体靶向治疗。