Nitric oxide (inhaled)

Medical gases
Medical gases

Inhaled gas that dilates only the lung vessels. It treats persistent pulmonary hypertension of the newborn; watch methaemoglobin and NO2.

Updated Nov 1, 2026

Also called: Inhaled nitric oxide (iNO)

Quick facts

Group: Medical gases
Target: Soluble guanylyl cyclase (sGC) in vascular smooth muscle
Used for: Term and near-term neonates
Key effects: Methaemoglobinaemia · Formation of nitrogen dioxide
Monitor: Continuous measurement · Methaemoglobin at baseline
ATC: R07AX01

No doses: the clinician sets them by the current guideline.

Mechanism of action

Soluble guanylyl cyclase (sGC) in vascular smooth muscleNitric oxide (inhaled)

The figure shows human soluble guanylyl cyclase in its NO-activated state; NO binds the haem iron (shown), but the NO molecule itself is not modelled in this structure.

Target in 3D: Soluble guanylyl cyclase (sGC) in vascular smooth muscle. PDB structure 6JT2 (RCSB PDB, public domain). View the structure at RCSB PDB

Inhaled NO diffuses from the alveoli into the smooth muscle of nearby pulmonary vessels, where it binds the haem of soluble guanylyl cyclase. The enzyme makes cyclic GMP, which lowers cytosolic calcium and relaxes the muscle. Because NO that reaches the blood is inactivated at once by haemoglobin, the effect stays in the lung: it dilates vessels next to ventilated alveoli, improves ventilation–perfusion matching and lowers pulmonary vascular resistance with little effect on systemic pressure.

Inhaled NO diffuses from ventilated alveoli into pulmonary vessel muscle
Activates soluble guanylyl cyclase: more cGMP
Smooth muscle relaxes: pulmonary vascular resistance falls
Haemoglobin inactivates NO in blood: little systemic effect

Indications

Term and near-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension of the newborn Persistent pulmonary hypertension of the newborn →
Acute vasodilator testing in pulmonary arterial hypertension (off-label), during right heart catheterisation Pulmonary hypertension and cor pulmonale →

Adverse effects

Common

Methaemoglobinaemia
Formation of nitrogen dioxide (NO2) in the circuit
Inhibition of platelet function and longer bleeding time
Atelectasis, noisy breathing or haematuria

Contraindications

Severe left ventricular dysfunction (relative): risk of pulmonary oedema

Key interactions

Sildenafil (PDE5 inhibitor): Acts on the same cGMP pathway; used with inhaled NO or during weaning to prevent rebound pulmonary hypertension.
High inspired oxygen: Speeds oxidation of NO to toxic NO2, and hyperoxia limits NO bioavailability (peroxynitrite formation).

What is monitored

Continuous measurement of inspired NO and NO2 with calibrated analysers
Methaemoglobin at baseline and at intervals during treatment
Oxygenation (PaO2, saturation, oxygenation index) to judge response
Blood pressure and signs of bleeding

Administration and safety

Delivered only through a dedicated system that measures NO and NO2 continuously, using certified gas cylinders.
The lowest effective concentration is used; it is weaned gradually, never stopped abruptly.
Avoid any interruption in delivery during transport or circuit changes.
If there is no response, it is stopped (with weaning) rather than continued.

Pregnancy and breastfeeding

Its approved use is in newborns; it is not a medicine used during pregnancy.

Nursing care

Record saturation and oxygenation before starting and after each change.
Check methaemoglobin and NO2 readings as scheduled and report high values.
During weaning, watch for falls in saturation, which signal rebound.
Keep the delivery system and its alarms checked.

Pharmacokinetics

Absorption: Inhaled through the ventilator or delivery system; acts within the lung.
Distribution: Inactivated quickly by haemoglobin, forming nitrosyl-haemoglobin and small amounts of methaemoglobin (reduced back by cytochrome b5 reductase).
Elimination: Mostly in the urine as nitrate.

Test yourself

Think of the answer, then tap the question to see it.

Why does inhaled nitric oxide dilate pulmonary but not systemic vessels?

NO entering the blood is inactivated at once by haemoglobin, so its action stays in the lung.

Which enzyme does NO activate in vascular smooth muscle?

Soluble guanylyl cyclase, which raises cGMP and relaxes the muscle.

Which two toxic products are monitored during inhaled NO therapy?

Methaemoglobin in the blood and nitrogen dioxide (NO2) in the inspired gas.

What happens if inhaled NO is stopped abruptly?

Rebound pulmonary hypertension with worsening hypoxaemia; it is weaned gradually.

Add to my cards (4)

Connections

← Back to the class: Medical gases

Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: Persistent Pulmonary Hypertension in the Newborn (Children (Basel), via PubMed Central, 2017); RCSB PDB - 6JT2: Structure of human soluble guanylate cyclase in the NO activated state (RCSB Protein Data Bank, 2019); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).

Spotted a mistake?We are always improving for the community. Tell us what is wrong and our team will review it.Report a mistake

Representative model, for educational purposes only.