Inhaled nitric oxide in adults: Biology and indications for use
- Jess Mandel, MD
Jess Mandel, MD
- Section Editor — Pulmonary Vascular Disease
- Professor of Medicine
- University of California, San Diego
Nitric oxide (NO) is a naturally occurring vasodilator. In patients with pulmonary arterial hypertension (PAH), inhaled NO has an established role in vasoreactivity testing. Inhaled NO has also been proposed as a long-term therapy for PAH and possibly other types of pulmonary hypertension (PH) , and is occasionally used as a rescue therapy for severely hypoxemic patients both with and without an established diagnosis of PH.
The role of inhaled NO in vasoreactivity testing and therapeutic uses of this agent in adults are discussed in this topic review. The use of inhaled NO in the management of infants with persistent PH and the role of exhaled NO in asthma and other chronic lung diseases are discussed separately. (See "Persistent pulmonary hypertension of the newborn", section on 'Inhaled nitric oxide' and "Exhaled nitric oxide analysis and applications".)
BIOLOGY AND PHARMACOKINETICS
Endogenous NO is produced from L-arginine in vascular endothelial cells by endothelial nitric oxide synthase (eNOS, type III NOS), a constitutively expressed enzyme . NO is a naturally occurring vasodilator that works with other molecules to determine vascular resistance (systemic and pulmonary) [3,4]. When administered by inhalation, it selectively dilates the pulmonary vasculature, is quick acting, and has a short half-life with minimal systemic symptoms, rendering it a suitable agent for vasoreactivity testing and therapy.
●Mechanism of action – NO induces smooth muscle soluble guanylate cyclase to increase cyclic guanosine monophosphate (cGMP). This reduces intracellular calcium levels, causing smooth muscle relaxation (ie, vasodilation) in precapillary resistance arterioles [2,5]. Additional effects of NO include suppression of both smooth muscle proliferation and platelet aggregation [6,7].
These properties have led to the development of inhaled NO and other agents that enhance local NO effects (eg, riociguat, a cGMP enhancer). There appears to be a threshold for pulmonary vasodilation when NO is administered by inhalation, which occurs at a dose of approximately 10 parts per million (ppm) [8-10]. Whether a dose-effect relationship exists has not been clearly defined. Administration of inhaled NO is discussed below. (See 'Procedure' below.)
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- BIOLOGY AND PHARMACOKINETICS
- PULMONARY ARTERIAL HYPERTENSION (GROUP 1)
- Vasoreactivity testing
- - Procedure
- - Efficacy
- ACUTE HYPOXEMIC RESPIRATORY FAILURE
- Patients with underlying pulmonary hypertension
- Patients without underlying pulmonary hypertension
- ADVERSE EFFECTS
- SUMMARY AND RECOMMENDATIONS