Nitric Oxide in Health and Disease of the Respiratory System

Abstract

During the past decade a plethora of studies have unravelled the multiple roles of nitric oxide (NO) in airway physiology and pathophysiology. In the respiratory tract, NO is produced by a wide variety of cell types and is generated via oxidation of l-arginine that is catalyzed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) have been shown to be modulators of bronchomotor tone. On the other hand, NO derived from iNOS seems to be a proinflammatory mediator with immunomodulatory effects. The concentration of this molecule in exhaled air is abnormal in activated states of different inflammatory airway diseases, and its monitoring is potentially a major advance in the management of, e.g., asthma. Finally, the production of NO under oxidative stress conditions secondarily generates strong oxidizing agents (reactive nitrogen species) that may modulate the development of chronic inflammatory airway diseases and/or amplify the inflammatory response. The fundamental mechanisms driving the altered NO bioactivity under pathological conditions still need to be fully clarified, because their regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways.

Redox-based regulation of signal transduction: Principles, pitfalls, and promises

“…Stimulation of growth factor receptors, toll like receptors (TLR), and cytokine receptors, also leads to the activation of signaling cascades that are regulated by hydrogen peroxide (H 2 O 2 ) as a result of activation of non-phagocytic oxidases (NOX), or dual oxidase (DUOX) (See Table 1) [18,19,[21][22][23][24]. The expression of multiple isoforms of these enzymes in a variety of tissues provides evidence that the deliberate production of low levels of oxidants is a feature of many cells [25].…”

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

“…NO might also be of importance in the influence of macrophages on immune responses in the lung. The debate about the possible beneficial and/or detrimental effect of NO still continues [35]. Initially, on the basis of the observation that asthmatics show elevated levels of exhaled NO, it was believed that an increased production of NO was considered to contribute to allergic disease in the lung.…”

Nitric Oxide: A Key Mediator of Biofilm Dispersal with Applications in Infectious Diseases

“…Side effects of nitrosative stress in host tissues include the generation of carcinogenic N-nitrosamines [106]. In the lungs, high levels of NO can transfer to the blood and cause methaemoglomia [107]. Recently the safety of delivery and the physiologic effects of intermittent exposure to 160 ppm NO gas three times daily for 30 min for 5 days have been assessed in clinical trials.…”