Reactive Oxygen Species-Reducing Strategies Improve Pulmonary Arterial Responses to Nitric Oxide in Piglets with Chronic Hypoxia-Induced Pulmonary Hypertension
Reactive Oxygen Species-Reducing Strategies Improve Pulmonary Arterial Responses to Nitric Oxide in Piglets with Chronic Hypoxia-Induced Pulmonary Hypertension
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DOI：
10.1089/ars.2012.4823
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发表时间：
2013-05-01
影响因子：
6.6
通讯作者：
Aschner, Judy L.
中科院分区：
文献类型：
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作者：
Fike, Candice D.;Dikalova, Anna;Aschner, Judy L.
目的：对于患有与缺氧相关的心肺疾病（例如患有慢性肺部疾病的婴儿）的慢性肺动脉高压，尚无有效的治疗方法。这些患者通常对吸入一氧化氮 (iNO) 治疗的肺扩张剂反应较差或不一致，原因不明。对 iNO 反应性差的一种可能解释是活性氧 (ROS) 和 NO 之间的相互作用导致 NO 生物利用度降低。我们的主要目的是确定减少 ROS 的策略是否可以改善慢性肺动脉高压新生仔猪模型阻力肺动脉 (PRA) 中 NO 供体 S-亚硝基-N-乙酰青霉胺 (SNAP) 的扩张反应。结果：慢性缺氧引起的肺动脉高压仔猪的 PRA 的 SNAP 扩张显着受损。 ROS 清除剂，包括降解过氧化氢 (H2O2) 的细胞渗透性和不可渗透性试剂，可改善长期缺氧仔猪 PRA 中 SNAP 的扩张。使用抑制一氧化氮合酶和 NADPH 氧化酶（ROS 的潜在酶源）的药物进行治疗，也可以改善缺氧仔猪 PRA 中 SNAP 的扩张。创新：我们的研究首次利用新生儿慢性肺动脉高压模型来评估多种潜在的ROS去除治疗策略对与肺血管阻力（PRA）调节最相关的血管中外源NO反应的影响。结论：旨在减少 ROS 的策略值得进一步评估和考虑，作为改善慢性肺动脉高压婴儿对 iNO 反应的治疗方法。抗氧化剂。氧化还原信号。 18, 1727-1738。
Aims: There are no effective treatments for chronic pulmonary hypertension in infants with cardiopulmonary disorders associated with hypoxia, such as those with chronic lung disease. These patients often have poor or inconsistent pulmonary dilator responses to inhaled nitric oxide (iNO) therapy for unknown reasons. One possible explanation for poor responsiveness to iNO is reduced NO bioavailability caused by interactions between reactive oxygen species (ROS) and NO. Our major aim was to determine if strategies to reduce ROS improve dilator responses to the NO donor, S-nitroso-N-acetyl-penicillamine (SNAP), in resistance pulmonary arteries (PRAs) from a newborn piglet model of chronic pulmonary hypertension. Results: The dilation to SNAP was significantly impaired in PRAs from piglets with chronic hypoxia-induced pulmonary hypertension. ROS scavengers, including cell-permeable and impermeable agents to degrade hydrogen peroxide (H2O2), improved dilation to SNAP in PRAs from chronically hypoxic piglets. Treatment with agents to inhibit nitric oxide synthase and NADPH oxidase, potential enzymatic sources of ROS, also improved dilation to SNAP in PRAs from hypoxic piglets. Innovation: Our studies are the first to utilize a newborn model of chronic pulmonary hypertension to evaluate the impact of a number of potential therapeutic strategies for ROS removal on responses to exogenous NO in the vessels most relevant to the regulation of pulmonary vascular resistance (PRA). Conclusions: Strategies aimed at reducing ROS merit further evaluation and consideration as therapeutic approaches to improve responses to iNO in infants with chronic pulmonary hypertension. Antioxid. Redox Signal. 18, 1727-1738.