Capsaicin-sensitive nerves and neurokinins modulate non-neuronal nNOS expression in lung

Prado, Carla M.; Leick-Maldonado, Edna A.; Miyamoto, Luciana; Yano, Larissa; Kasahara, David I.; Martins, Mílton A.; Tibério, Iolanda de Fátima Lopes Calvo

doi:10.1016/j.resp.2007.08.004

Cited by 9 publications

(9 citation statements)

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“…Previously, we have already shown that the mainly cells present in airway walls of this asthma model are eosinophils, CD4+ lymphocytes, iNOS and nNOS positive cells [4,6,24,28]. In addition, we had demonstrated in distal lung of this animal asthma model that eosinophil density, iNOS positive cells and isoprostane PGF2α were increased due to the effect of the sensitization process.…”

Section: Discussionmentioning

confidence: 74%

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Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

et al. 2013

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BackgroundThe importance of the lung parenchyma in the pathophysiology of asthma has previously been demonstrated. Considering that nitric oxide synthases (NOS) and arginases compete for the same substrate, it is worthwhile to elucidate the effects of complex NOS-arginase dysfunction in the pathophysiology of asthma, particularly, related to distal lung tissue. We evaluated the effects of arginase and iNOS inhibition on distal lung mechanics and oxidative stress pathway activation in a model of chronic pulmonary allergic inflammation in guinea pigs.MethodsGuinea pigs were exposed to repeated ovalbumin inhalations (twice a week for 4 weeks). The animals received 1400 W (an iNOS-specific inhibitor) for 4 days beginning at the last inhalation. Afterwards, the animals were anesthetized and exsanguinated; then, a slice of the distal lung was evaluated by oscillatory mechanics, and an arginase inhibitor (nor-NOHA) or vehicle was infused in a Krebs solution bath. Tissue resistance (Rt) and elastance (Et) were assessed before and after ovalbumin challenge (0.1%), and lung strips were submitted to histopathological studies.ResultsOvalbumin-exposed animals presented an increase in the maximal Rt and Et responses after antigen challenge (p<0.001), in the number of iNOS positive cells (p<0.001) and in the expression of arginase 2, 8-isoprostane and NF-kB (p<0.001) in distal lung tissue. The 1400 W administration reduced all these responses (p<0.001) in alveolar septa. Ovalbumin-exposed animals that received nor-NOHA had a reduction of Rt, Et after antigen challenge, iNOS positive cells and 8-isoprostane and NF-kB (p<0.001) in lung tissue. The activity of arginase 2 was reduced only in the groups treated with nor-NOHA (p <0.05). There was a reduction of 8-isoprostane expression in OVA-NOR-W compared to OVA-NOR (p<0.001).ConclusionsIn this experimental model, increased arginase content and iNOS-positive cells were associated with the constriction of distal lung parenchyma. This functional alteration may be due to a high expression of 8-isoprostane, which had a procontractile effect. The mechanism involved in this response is likely related to the modulation of NF-kB expression, which contributed to the activation of the arginase and iNOS pathways. The association of both inhibitors potentiated the reduction of 8-isoprostane expression in this animal model.

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Section: Discussionmentioning

confidence: 74%

“…This approach was chosen based on previous data [6,24,25]. As high doses of 1400 W (50 mg/kg ip ) can cause toxic effects, we chose a lower dose with previously demonstrated proven therapeutic efficacy in experimental models [7,25].…”

Section: Methodsmentioning

confidence: 99%

Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

et al. 2013

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“…Corroborating the interaction between nitric oxide and neurokinins, our group showed that capsaicin-sensitive sensory nerve fibers and neurokinins modulate nonneuronal nNOS expression by inflammatory and respiratory epithelial cells [108]. This increase in nNOS expression was also maintained for 14 days after capsaicin treatment and correlated with pulmonary mechanical reduction observed after capsaicin treatment when the lung content of neurokinin was already reduced [109].…”

Section: Airway Hyperresponsivenessmentioning

confidence: 99%

Nitric Oxide in Asthma Physiopathology

2011

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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. Animalin vivostudies 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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“…Whatever the fine mechanisms involved, however, inflammatory infiltration phenomena with increased blood flow and vascular permeability, along with the accumulation of fluid (extravasation), represent common features. This is due to the fact that recruited monocytes/macrophages are highly sensitive to bacterial and non-bacterial stimuli and function as a principal source of proinflammatory cytokines (22). These are groups of polypeptides that play a pivotal role in orchestrating the inflammatory response, further increasing the cellular infiltration and cellular activation (26,27), but also inducing defensins in respiratory tract epithelial cells (28).…”

Section: Discussionmentioning

confidence: 99%

“…When considering a non-infectious pharyngitis model, the capsaicin-induced model is widely used since capsaicin is known to bring about the activation of primary afferent sensory neurones and the release of neuropeptides, such as substance P and neurokinin A, from nerve endings (22). These neuropeptides possess strong proinflammatory effects in the airway tissues, leading to increased vascular permeability and plasma extravasation (23).…”

Section: Effect Of Vbc-1814/7j a Poly-phytocompound On A Non-infectmentioning

confidence: 99%

Effect of VBC-1814/7J, a poly-phytocompound, on a non-infectious model of pharyngitis

Uemura¹,

Nagpal

Zerbinati

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Pharyngitis presents as an inflammation of the oropharynx, and clinical examination often shows evidence of nasopharyngitis. In numerous cases the condition occurs as a self-limiting illness of non-infectious aetiology, whose clinical management remains a matter for debate given the inappropriateness of antibiotics, the reported worsening following steroid use and the recent discouragement of the use of Chinese herbal medicine. The aim of the present study was thus to test VBC-1814/7J, a poly-phytocompound with known anti-inflammatory and immune-response enhancing properties, in an experimental model of non-infectious pharyngitis. Experimental non-infectious pharyngitis was induced by applying a pyridine solution to the surface of the pharyngeal mucosa in rats that were either normally fed (group A) or fed VBC-1814/7J three days prior to and three days subsequent to the induction of pharyngitis (group B). Healthy rats treated with topical saline were used as a control (group C). At time-points of 0, one hour, one day and three days sacrifices were carried out and microscopic examination, Evans blue (EB) dye extravasation and tissue concentrations of tumour necrosis factor (TNF)-α, interleukin (IL)-6 and mRNA of α-and β-defensins were studied. As compared with group C, group A showed significant microscopic damage, EB extravasation, and increases in the levels of TNF-α and IL-6, as well as in the mRNA of three defensins (P<0.001) on the third day of observation. VBC-1814/7J significantly mitigated these microscopic and inflammatory markers while allowing a prompter and wider defensin reaction (P<0.05 vs. group A). These data suggest that VBC-1814/7J, as demonstrated in earlier studies, has the potential to address non-infectious pharyngitis in clinical practice.

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Capsaicin-sensitive nerves and neurokinins modulate non-neuronal nNOS expression in lung

Cited by 9 publications

References 27 publications

Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

Modulation of the oscillatory mechanics of lung tissue and the oxidative stress response induced by arginase inhibition in a chronic allergic inflammation model

Nitric Oxide in Asthma Physiopathology

Effect of VBC-1814/7J, a poly-phytocompound, on a non-infectious model of pharyngitis

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