ECB-ART-42893
ISRN Allergy
2011 Apr 19;2011:832560. doi: 10.5402/2011/832560.
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Nitric oxide in asthma physiopathology.
Prado CM
,
Martins MA
,
Tibério IF
.
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Asthma is a chronic inflammatory airway disease characterized by allergen-induced airway hyperresponsiveness, airway inflammation, and remodeling. Nitric oxide (NO) derived from constitutive and inducible enzymes affects many aspects of asthma physiopathology. Animal in vivo studies have indicated that inhibition of iNOS may play a central role in the modulation of these features, particularly extracellular matrix remodeling. Additionally, increases in iNOS-derived NO, observed in asthmatic patients, may lead to an increase in peroxynitrite and an imbalance of oxidant and antioxidant pathways. In addition, endogenous nitric oxide produced by constitutive enzymes may protect against the remodeling of the lung. Therefore, nitric oxide donors and/or iNOS inhibitors may have therapeutic potential in asthma treatment and can also be used with corticosteroids to counteract airway remodeling. This paper focuses on the pathophysiological role of nitric oxide, mainly derived from inducible isoforms, in the various pathologic mechanisms of allergic asthma and the importance of nitric oxide and/or arginase inhibitors in asthma treatment.
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Genes referenced: LOC115919910 LOC590297
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Figure 1. L-arginine, the common substrate to both the nitric oxide synthase and the arginase pathway. L-arginine is catalyzed by both arginase and nitric oxide. Arginase produces L-ornithine and urea that can act in various organs. In contrast, nitric oxide can be produced by both constitutive (cNOS) and inducible (iNOS) nitric oxide synthases and have pathophysiological roles important in health and diseases via the direct or indirect effects on oxidative stress production. Thus, arginase regulates the production of NO, and NO regulates the activity of arginase by substrate competition. |
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Figure 2. The dual effects of nitric oxide in asthma pathology. In asthma, nitric oxide can have both beneficial and adverse effects. The production of NO by constitutive isoforms can relax the smooth muscle of airways and vessels via cyclic GMP regulation inducing bronchodilation and vasodilation. However, by acting in the postcapillary venule, it can induce plasma extravasation. Nitric oxide can also regulate the mucosal glands, increasing the mucus secretion. High amounts of nitric oxide produced by iNOS in pathological situations induce the inflammatory cell chemotaxis, particularly recruiting eosinophils and T-lymphocytes to the lung. The reaction of nitric oxide with anion superoxide increases the oxidative stress pathway and can induce cellular injury by protein dysfunction or DNA injury and airway hyperresponsiveness. By substrate competition, nitric oxide can control the arginase pathway and induces airway remodeling, smooth muscle contraction and mucus production. |
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