Neurokinins and inflammatory cell iNOS expression in guinea pigs with chronic allergic airway inflammation

Abstract

In the present study we evaluated the role of neurokinins in the modulation of inducible nitric oxide synthase (iNOS) inflammatory cell expression in guinea pigs with chronic allergic airway inflammation. In addition, we studied the acute effects of nitric oxide inhibition on this response. Animals were anesthetized and pretreated with capsaicin (50 mg/kg sc) or vehicle 10 days before receiving aerosolized ovalbumin or normal saline twice weekly for 4 wk. Animals were then anesthetized, mechanically ventilated, given normal saline or N G -nitro-L-arginine methyl ester (L-NAME, 50 mg/kg ic), and challenged with ovalbumin. Prechallenge exhaled NO increased in ovalbumin-exposed guinea pigs (P Ͻ 0.05 compared with controls), and capsaicin reduced this response (P Ͻ 0.001). Compared with animals inhaled with normal saline, ovalbumin-exposed animals presented increases in respiratory system resistance and elastance and numbers of total mononuclear cells and eosinophils, including those expressing iNOS (P Ͻ 0.001). Capsaicin reduced all these responses (P Ͻ 0.05) except for iNOS expression in eosinophils. Treatment with L-NAME increased postantigen challenge elastance and restored both resistance and elastance previously attenuated by capsaicin treatment. Isolated L-NAME administration also reduced total eosinophils and mononuclear cells, as well as those cells expressing iNOS (P Ͻ 0.05 compared with ovalbumin alone). Because L-NAME treatment restored lung mechanical alterations previously attenuated by capsaicin, NO and neurokinins may interact in controlling airway tone. In this experimental model, NO and neurokinins modulate eosinophil and lymphocyte infiltration in the airways. nitric oxide; inducible nitric oxide synthase; asthma; lymphocytes; eosinophils NEUROKININS such as substance P and neurokinin A are involved in the modulation of several aspects of inflammatory responses in the lungs. These peptides induce airway smooth muscle contraction, peribronchial edema, and airway mucous secretion and are considered mediators of the excitatory nonadrenergicnoncholinergic response (43). It has been previously shown that substance P and neurokinin A play significant roles in priming eosinophils and in lymphocyte recruitment in allergic lung inflammation (33,43,44). In guinea pigs and other mammals, pretreatment with capsaicin has been used as a research tool to elucidate the physiological effects of neurokinins (18,29). It has been previously show that administration of high doses of capsaicin reduces tissue concentrations of substance P and other neurokinins (28,29).Nitric oxide (NO), a gaseous molecule that is generated during the conversion of the amino acid L-arginine to Lcitrulline by NO synthase (NOS), is considered a mediator of the inhibitory nonadrenergic-noncholinergic response (3,26,32). The role of NO in the modulation of allergic inflammation and bronchial hyperresponsiveness is currently unclear. There is some evidence that NO has both inflammatory and antiinflammatory effects in experimental models of ai...

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

“…Cells labeled for iNOS in the alveolar septa were counted in 20 non-coincident fields enlarged to 1000X using the point-counting technique with a reticule of known area, overlaid on the eyepiece of the microscope (21).…”

Efeito do inibidor de proteinase de origem vegetal EcTI, sobre a lesão pulmonar induzida pela elastase em camundongos C57BI6

“…Sua produção é estimulada por algumas citocinas como o TNF-, IL-1 e IFN- (Moncada, 1993;Moncada et al, 1991), além do polissacarídeo bacteriano. A iNOS é a maior responsável pela produção de NO e parece estar presente principalmente em condições patológicas (Prado et al, 2005).…”

“…Resultados de nosso grupo de pesquisa demonstraram uma importante participação do óxido nítrico em modelo experimental de asma (Prado et al, 2005(Prado et al, , 2010 (Takahashi et al,1992).…”

“…De acordo com Prado et al (2005) e Prado et al (2010), o óxido nítrico exerce importante papel na fisiopatologia da asma, com aumento da expressão de iNOS em eosinófilos e células linfomononucleares presentes nas vias aéreas distais de animais sensibilizados. Ainda, estes mesmos autores mostraram que a isoforma nNOS, embora constitutiva, encontra-se presente em células inflamatórias (linfomononucleares e eosinófilos) (Prado et al, 2003).…”

Efeitos dos inibidores de NF Kappa-B e Rho Quinase em um modelo de asma animal: comparação com o tratamento com corticosteroides

“…As isoformas constitutivas estão envolvidas na vasodilatação e broncodilatação. A produção de iNOS é estimulada por muitas citocinas pró-inflamatórias e é expressa em alguns tipos de células inflamatórias (Ricciardolo et al 2004;Prado et al, 2005b).…”