There are several pulmonary hypertensive diseases that affect the neonatal population, including persistent pulmonary hypertension of the newborn (PPHN) and bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH). While the indication for inhaled nitric oxide (iNO) use is for late-preterm and term neonates with PPHN, there is a suboptimal response to this pulmonary vasodilator in ~40% of patients. Additionally, there are no FDA-approved treatments for BPD-associated PH or for preterm infants with PH. Therefore, investigating mechanisms that alter the nitric oxide-signaling pathway has been at the forefront of pulmonary vascular biology research. In this review, we will discuss the various mechanistic pathways that have been targets in neonatal PH, including NO precursors, soluble guanylate cyclase modulators, phosphodiesterase inhibitors and antioxidants. We will review their role in enhancing NO-signaling at the bench, in animal models, as well as highlight their role in the treatment of neonates with PH.

中文翻译：

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在新生儿中增强肺血管NO信号的疗法。

有几种会影响新生儿的肺动脉高压疾病，包括新生儿持续性肺动脉高压（PPHN）和支气管肺发育不良（BPD）相关的肺动脉高压（PH）。虽然吸入一氧化氮（iNO）的适应症适用于PPHN的早产和足月新生儿，但约40％的患者对此肺血管扩张药的反应欠佳。此外，尚无FDA批准的BPD相关PH或PH早产儿的治疗方法。因此，改变一氧化氮信号通路的研究机制一直处于肺血管生物学研究的前沿。在这篇评论中，我们将讨论新生儿PH的各种机制途径，包括NO前体，可溶性鸟苷酸环化酶调节剂，磷酸二酯酶抑制剂和抗氧化剂。我们将在动物模型中回顾它们在增强NO信号传导中的作用，并重点介绍它们在PH新生儿治疗中的作用。