**Abstract**

Since the discovery of nitric oxide (NO) as a physiological substance produced in the endothelium, the impairment of endothelial NO production and reactivity of the pulmonary vasculature to NO have been described in animal models and patients with pulmonary hypertension (PH). The NO synthase-NO-cyclic guanosine monophosphate (cGMP) pathway is impaired in pulmonary arterial hypertension (PAH), pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis (PCH), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Pioneering clinicians conceived that NO can be administered to the lung by inhalation and used this strategy to treat PH in humans and acute hypoxic PH in animal models. Inhaled NO (iNO) selectively decreases pulmonary arterial pressure with no changes in systemic arterial pressure. When iNO diffuses into the blood, it is converted to NO3 <sup>−</sup>, thereby losing its vasodilatory effects. NO might then be recycled in hypoxic remote organs, where NO3 <sup>−</sup> and NO2 <sup>−</sup> are reduced to NO. In the present chapter, the metabolic fate of iNO, based on previous air pollution research in Japan, is discussed. Then, we describe recent clinical applications of iNO in pediatric patients with various diseases, including bronchopulmonary dysplasia (BPD), persistent PH of neonates, and congenital diaphragmatic hernia (CDH). We also summarize the role of iNO in the catheterization lab, including acute vasoreactivity testing to assess prognosis, indications for specific PH therapy, and operability of congenital heart disease.

**Keywords:** nitric oxide inhalation, pulmonary hypertension, metabolism of nitric oxide, nitrate, pediatric, neonate
